15 Jun An Inside Look at Glucose Clamp studies in Diabetes Patients

High Point Clinical Trials Center is a recognized Center of Excellence for Metabolic research offering industry leading Patient recruitment via innovative outreach initiatives, an active database of 6000+ Patients with Diabetes and extensive experience executing complex clinical pharmacology studies.

Clayton Dehn, VP of Clinical Pharmacology Services

We have invested significantly in medical, scientific and technical resources to meet the ever-evolving needs of our Sponsors. Clayton Dehn, our Vice President of Clinical Pharmacology Services, has a vast background in metabolic disorders and in-depth knowledge in the planning and conduct of glucose clamp studies.  Below, he lays out the rationale behind glucose clamps, the different methodologies and how these studies relate to diabetes medications. 

A brief introduction to glucose clamps:

If you have worked in the Metabolic disorders space or for a biopharmaceutical company focusing on the development of treatments for Diabetes, obesity or Fatty liver, there is a high probability that you’ve encountered the term “glucose clamps”. What is a clamp and what is its purpose? What do these studies represent? What types of clamps are commonly used and what is the objective of each one? What do the results indicate and how are they used? What are the complexities and risks associated with these studies and how is participant safety assured?

What are glucose clamps?

At their core, glucose clamps are infusion-based tests that in some way interrupt the insulin-glucose feedback loop. These procedures offer no therapeutic value. Although they could arguably offer some diagnostic insight, that utility is restricted by the esoteric complexity of the tests limiting their practical implementation into clinical practice. Glucose clamps are, however, incredibly valuable research methodologies that are exquisitely reproducible within an individual when testing occurs under similar and tightly-controlled conditions. This means that baseline testing compared to post-interventional testing offers strong confidence that any differences observed can be associated with the intervention and that changes from baseline can be detected in smaller study populations.

Incidence of Diabetes and Pre-Diabetes in North Carolina

What are the different types of glucose clamps and how do they work?

There are many types of clamp procedures, and they can tell us different things.

Quantification of Insulin Sensitivity:

The classic glucose clamp is the hyperinsulinemic-euglycemic clamp, which is the gold-standard measure of insulin sensitivity. In this test, insulin is infused to artificially increase the circulating concentration to physiologically relevant levels, usually replicating peak post-prandial insulinization. The normal physiological response to this hyperinuslinization is the suppression of both endogenous insulin and glucose production as well as peripheral glucose uptake. The net effect should be a decline in blood glucose, but this is prevented with intense glucose monitoring and adjustment of a variable counter-infusion of glucose. The glucose infusion rates required to maintain the target blood glucose represents the subject’s sensitivity to insulin, whereby those requiring a higher glucose infusion are more sensitive to insulin than those who require less.

It is important to note that although the hyperinsulinemic-euglycemic clamp can be performed in insulin-resistant populations to demonstrate a therapeutic response to an insulin-sensitizing agent, it does require additional consideration. Insulin resistance also affects the liver and endogenous glucose production is dysregulated in this population. The exogenous insulin infusion may be inadequate to achieve full suppression of endogenous glucose production. Enriching the glucose infusion with a stable isotope of glucose may be necessary to quantify any residually unsuppressed hepatic glucose production that may be contributing to the glycemic control during the clamp procedure.  

Quantification of beta cell response:

Many antidiabetic medications under investigation and on the market are insulin secretagogues. The therapeutic approach of overwhelming insulin resistance by stimulating endogenous insulin release has evolved in sophistication from agents associated with a high risk of hypoglycemia such as sulfonylureas to those that avoid hypoglycemia by depending upon hyperglycemia to co-stimulate insulin release. These features and ability to stimulate the beta cells to increase insulin release are easily characterized with a type of glucose clamp called a hyperglycemic glucose clamp. In this type of clamp, glucose is infused to achieve an elevated target blood glucose. Insulin, glucose infusion rates, and glycemia can be evaluated as estimates of post-therapeutic response. As an alternative to hyperglycemic glucose clamps, graded glucose infusions, which are clamp-like procedures in which glucose is infused at progressively increasing but fixed rates for set periods of time, can be used to characterize beta cell response.

Time-Action Profiles

Time-action profile clamps are used to describe the activity of insulin products. In these clamps, the investigational insulin product is administered as it is intended to be used therapeutically, a subcutaneous injection for example. Dextrose is infused to counter the glucose-lowering effects of the insulin product. From the changing rate of glucose infusion required to maintain the glycemic target the onset, peak, duration, and offset of the insulin product can be determined. 

Do glucose clamping and diabetes medications work together?

Glucose clamps are an important test for developing some antidiabetic medications, not every diabetes medication needs to be tested with glucose clamps. For example, glucose clamp testing glucose-independent insulin secretagogues, such as the sulfonylureas, would not be very informative as these agents do not act in pathways that can be elucidated by the glucose clamp.

New medications to treat diabetes must go beyond improving glycemic control. Innovation in antidiabetic drug development is stifled by how crowded the market is with effective approved medications, and by the cost associated with the relatively recent (2008) requirement for thorough cardiovascular risk assessment. For drug developers looking to address the unmet need for antidiabetic medications with acceptable safety profiles that improve insulin sensitivity, glucose clamps are all but prerequisite.

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07 Mar The Importance of Building Relationships in Clinical Trial Recruitment Operations

A few months ago, a lady suffering from diabetes and obesity reached out to our recruitment team. Her health was declining, and she was not disciplined with her nutrition or medication regiment. Farid Zeatar, our Director of Recruitment Operations, proposed a clinical study to her that not only could bring benefit to her condition but also allow her to get guidance from our Medical Team throughout the study along with useful advice on how to better manage her condition.

She accepted to explore joining the study and visited our research facility for a screening appointment, and beyond the benefit of the investigational product, her interactions with our Medical Team set her on the right path. She continued progressing even after the study, and Farid still remains in touch with her today. She knows that while we are not a healthcare provider, our Medical Team remains at her service to help mitigate the gaps and discuss the study she participated in. She can also visit with our Physicians volunteering at the community clinic.

This story sums up what recruitment is all about – the relationship with Patients – which Farid and the HPCTC Medical Team prioritize day-in and day-out.

Farid joined our team in 2010 and has ever since been involved in forming relationships within the community and spreading the word on the benefits of clinical research. His main mandate is to ensure that we meet our recruiting commitments, and he has built a team that uses a multifaceted approach to do so.

His philosophy is to leverage the latest technology available without neglecting the critical interpersonal relations and 1-on-1 approach. While a segment of recruitment relies on filtering participants in our Clinical Trial Management System, or speaking with potential participants on the phone, it does not stop there. A crucial component is participating in community events – getting face-to-face with fellow citizens interested in clinical research – and even engaging with people on social media. It’s also about keeping in contact with participants well beyond the completion of the study if needed.

In the recruitment field, you never know who you may encounter in a given week, which is why it’s more important than ever to be well-versed in different cultures, perspectives and communication methods. Having lived in many countries before settling down in the Piedmont Triad area in 1982, Farid has learned the art of understanding culture and character, and he combines that asset with an excellent knowledge of the demographics in NC.

What are patients looking for? Sure, financial compensation always plays a part, but no one is looking for a team of robots to interact with. We want real people who we can communicate with, who can understand our needs, who will make us feel valued and who we can trust. Farid and his recruitment team make this their top priority.

As Farid mentions:

“I have always been very receptive to the expectations of Study participants regarding trust, safety and medical expertise. In my experience, Patients join studies not only for the financial benefit but also for the possibility of obtaining a highly reliable assessment of their health and helping progress new promising therapies to the market. I favor open communication regarding study rationale and treatment details, requirements as well as obligations and expect my recruitment team to do so in all their interactions.”

Farid is a big supporter of 1-on-1 discussions between members of High Point CTC’s Medical Team and Participants. This cultivates trust and eliminates communication gaps.

Farid then adds, “Beyond the financial compensation, Participant safety, the reputation of the research facility and the expertise of the staff will always lead to better compliance and study completion rates. The best way to achieve this is by working closely with our Participants and making sure they understand the important contribution they are making towards the development of promising new therapies.”

At the end of the day, it’s about you – the Participants. It’s not about us.

Our Study Participants, whether they be Healthy volunteers or Patients seeking new treatment options, are actively contributing to the advancement of medical knowledge and are directly responsible for the development of new promising therapies for many unmet medical needs. We are thankful for their trust and contribution and share their commitment to the miracle of medicine.

Want to speak with a member of our team about an upcoming study? Contact us at  rcenter@highpointctc.com or head to https://highpointctc.com/studies/ to learn more and register for an upcoming clinical trial.

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15 Sep Medical Volunteering: Bringing Patients Closer to Research

The Community Clinic of High Point (CCHP) is a small building on North Main Street in downtown High Point, NC. Although many residents drive past it each day, a large percentage is likely unfamiliar with what happens inside. Little do they know, over sixty medical physicians and staff volunteer their time each month to offer highly needed medical support.

Dr. Jonathan Austin MD, Principal Investigator

Dr. Jonathan Austin, Principal Investigator at High Point Clinical Trials Center (HPCTC), is one of the many medical professionals who volunteer at the clinic each week. His objective is to combine his extensive medical experience as well as the services of HPCTC to improve the lives and well-being of the medically underserved.

Dr. Austin discusses his experience at the Community Clinic:

“Patients come to me with a mixture of established and acute care conditions involving diabetes, high blood pressure, depression, or just general health screening. It is a busy time, but the Patients are appreciative of the care and are inquisitive about their health. Often, there are opportunities to discuss their health challenges in more detail and begin a discussion about potential research options if desired. Most recently, I discussed studies involving psoriasis, diabetes, obesity, NASH/NAFLD and COPD with my patients.”

“I have also started a Chronic Obstructive Pulmonary Disease initiative to identify this frequently underdiagnosed condition by providing free spirometry screenings. My goal is to educate about the effects of smoking, offer cost effective treatments and introduce patients to potentially beneficial research studies before the condition advances to a life-threatening stage. Further, we partnered with iCardiac to secure an EKG technology that allows the community clinic to perform EKGs on site.

Finally, we are creating a database that gives a clearer picture of disease states in our local community. For instance, we have finished a NASH/NAFL chart review and will begin a renal impairment database this month.”

One intriguing yet complex aspect of working at the clinic is evaluating potential drug-drug interactions for patients on multiple medications. As Dr. Austin explains, many Patients are taking multiple medicines for their chronic conditions and the challenge is often identifying what medications are truly needed and how to benefit from them without unwanted interactions or side effects.

“This is certainly an area where health care providers are balancing the therapeutic benefits of a medication against potential drug-drug interactions or unexpected side effects. The pharmacokinetic and pharmacodynamic effect of an illicit substance on a medication or of a certain molecule on another can alter the expected health outcomes completely. Once again, clinical research provides critical insight on drug-drug interactions and the risks associated with them. The combination of this information with the provision of services at the community clinic can only bring value to the Patients we see every week.”

Whether it is the issue of polypharmacy, diabetes, liver disease or COPD, combining the capabilities of a premier clinical pharmacology unit like High Point Clinical Trials Center with the service of the Community Clinic can bring significant value to Patients and help them better manage their chronic or acute conditions. As a means of expanding this dialogue between healthcare providers and underserved Patients, HPCTC will also continue to offer services throughout the community, whether at the Community Clinic or with its new health center on wheels – a mobile unit that allows for remote screening and the provision of medical procedures throughout North Carolina.

You can visit HPCTC’s website to learn more about the company’s community outreach as well as the very innovative the mobile unit platform.

Established approximately 22 years ago, the CCHP belongs to the North Carolina Association of Free and Charitable Clinics and is one of 81 clinics located throughout North Carolina. The clinic welcomes uninsured individuals and provides excellent preventative care with full lab panels and screenings treating patients for mental illnesses like depression and chronic illnesses such as diabetes.

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22 Jun Looming Epidemics: Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH)

Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are looming epidemics and currently the intense focus of the academic, pharmaceutical and medical industry.

Dr. Margarita Nuñez, Medical Director/Principal Investigator at High Point Clinical Trials Center, elaborates on this epidemic and how reaching out to the community is a crucial component of tackling this growing issue.

Dr. Margarita Nunez, Medical Director

As Dr. Nuñez shares, there have always been concerns with the complications that come with diabetes, but one of the common issues that went undiagnosed for a while—even in clinical settings—was an elevation in patients’ liver enzymes.

“Over time, experts in the medical field began to recognize the damage to the liver that comes from and is caused by metabolic abnormalities. It used to be assumed that individuals with abnormal liver enzymes were “closet drinkers.” However, a number of patients would never drink at all, which led experts to further investigate liver damage and its connection to diabetes and metabolic disorders,” she explains.

Dr. Nunez continues “Initially, when presented with a patient experiencing damage to the liver, doctors would typically use an ultrasound to check for illnesses like Hepatitis, but in several cases, they often assumed it was a viral issue. Now, doctors and researchers have since been able to identify this condition as Non-Alcoholic Fatty Liver Disease (NAFLD) that can progress to Non-Alcoholic Steatohepatitis (NASH) and even Cirrhosis. NAFLD is described as fatty infiltration of the liver without evidence of inflammation, whereas NASH refers to fatty infiltration of the liver with the presence of inflammation.”

“It is imperative to understand that NAFLD and NASH are conditions that cannot be taken lightly. The damage to the liver is a real medical problem that in many cases can be life threatening. What is even more alarming is that victims of this disease typically do not even know they have it—in fact, it can go undetected for years. Therefore, bringing awareness to the condition within the community is of utmost importance.”

So, what is the best way to treat people who have this underlying liver damage?

Dr. Nuñez points out, “Like many metabolically related diseases, the current recommendation is lifestyle modification. However, while poor dietary choices and lack of exercise heavily contribute, there is evidence to suggest underlying genetic factors could affect metabolism of fats and lipids, leading to the accumulation of fatty deposits in the liver.”

Therapies are under development for both diseases, but currently there are no approved drugs to treat them. So, for now, the major effort must be directed towards patient education, and most importantly the positive impact that can be made through early diagnosis.

Dr. Nuñez emphasizes, “It’s really important to identify the problem even if there is no cure. Realistically, there is something you can do to make a difference. You can change your lifestyle and try to improve your parameters. Patients with this condition could also be entering into research to potentially help people in the future or they could join a clinical trial for possible treatment.”

NAFLD affects anywhere from 6-35% of people in the United States and refers to the presence of fat after other causes for secondary fat have been ruled out, including heavy alcohol use. Risk factors for this condition include obesity, Type 2 Diabetes, Dyslipidemia and Metabolic Syndrome. NASH, on the other hand, affects approximately 3-5% of people in the United States, diagnosed by hepatic inflammation via biopsy or fibroscan, or a confluence of other non-invasive metabolic parameters.

High Point Clinical Trials Center (HPCTC) works in the North Carolina and more specifically the Piedmont Triad region to help the community understand NAFLD and NASH or its emerging stages. Dr. Nunez explains, “We have been developing a screening initiative to invite people who are concerned about NASH or potential liver injury to come in, and we will do some basic tests and discuss the results.”

In addition to the screening initiative, HPCTC’s medical staff volunteer at the Community Clinic of High Point to help identify patients who could benefit from intervention and bring awareness to the problems they are encountering. The center has also recently launched a 33’ Recreational Vehicle (RV), “health center on wheels,” designed to support a wide range of screenings and bringing mobility to the outreach effort by expanding the bandwidth to the entire Triad region and beyond.

These initiatives are a critical first step in the journey towards raising patient awareness and helping advance promising new therapies to the market.

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29 Apr Medical Volunteering: An Investment in Positive Health Outcomes

In a recent blog the very important role of the Principal Investigator was described and we provided information on what clinical research is. Beyond their day to day involvement at High Point Clinical Trials Center, Physician Investigators, Dr. Jonathan Austin and Dr. Mark Pearson, are also involved in the community and have participated in other volunteer medical initiatives both domestically and overseas. These activities not only provide healthcare services to the medically underserved but they serve as an educational opportunity where Patients learn about clinical trial research and evolving new therapies.

Dr. Mark Pearson MD, Sub-Investigator

Dr. Jonathan Austin MD, Principal Investigator

Dr. Austin and Dr. Pearson have been adamant about participating in community-based medicine and supporting Patients who may not have the financial resources to access primary and preventative medical services otherwise. For example, their involvement at the Community Clinic of High Point (CCHP) allows them to offer care in an outpatient setting to those with acute or chronic medical conditions and limited means of accessing healthcare. Patients with little or no insurance and low income are treated at CCHP by an expert group of volunteer physicians from all walks of medicine who generously donate their time and skills to make a difference in the lives of their neighbors.

Dr. Austin has initiated a screening program for evaluation of Chronic Obstructive Pulmonary Disease (COPD) in Patients by symptom driven surveys with state of the art spirometry assessments. Additionally, he has also teamed with iCardiac, a leading core laboratory for cardiac safety testing. Their cardiac technology will enable high quality bedside EKGs to be obtained from Patients along with iCardiac’s cardiologist assessments to guide subsequent Patient care.

Dr. Pearson has volunteered overseas doing medical and surgical work at a Missionary Hospital In southern Nigeria for several years, then moved to and worked doing Medical outreach and education for 6 years in northern Haiti from 2000 to 2006. He also recently completed a Fellowship at LSU, New Orleans in Undersea & Hyperbaric Medicine and Wound Care.

The importance and benefits of clinical research have been demonstrated repeatedly and across several therapeutic areas. Experimental therapies have provided tangible benefits to Patients suffering from debilitating and chronic conditions and the involvement of physicians within the community is important to provide Patients with the necessary information and address their questions first hand as to what clinical research is and how it can potentially benefit them.

Only by giving back to our community and sharing opportunities for Patients to benefit from clinical research can the progress in both novel treatment development and Patient care continue.

The High Point Clinical Trials Center Medical Team can be reached directly at medicalteam@highpointctc.com

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09 Dec What is the role of a PI?

When I first saw the abbreviation “PI” I paused to think what or who is a PI?–private investigator, physician investigator, personal injury lawyer?  I came to find out that “PI” in the clinical research world stands for Principal Investigator.

In terms of the major players in a clinical research trial,  principal investigators assume ultimate responsibility  for the conduct of a clinical research study.  That being said, an investigator cannot be in all places at all times so research tasks may be delegated to research staff and the investigator must maintain oversight for the conduct of those to whom they delegate these duties.  Again, they are responsible for the ethical conduct and supervision of the trial and will protect the rights, safety and welfare of the volunteers.

Also, an investigator ensures that research volunteers are informed of a study appropriately and that they are aware that the study treatment is being used for research purpose–this is known as informed consent and follows a continuum throughout the study.   If any changes are made to the study protocol, it is the responsibility of the PI to fully inform the volunteers of these changes and offer an option for them to discontinue the study if they wish.  Furthermore, the  PI is the voice for the research site when there are patient care issues that warrant notification of the sponsor or ethics committees (IRB).  .  Again, the rights, safety and welfare of the research volunteers are the number one priority of the investigator.   Medical assessments, efficacy evaluation of the research drug and determining whether the therapy is related to adverse events are further commitments of an investigator. Finally, transparency in terms of providing accurate data are yet another important duty of the PI.

Who can become a PI? 

An investigator does not necessarily have to be a physician or PhD in a particular field, but should be qualified by education, training and experience to assume responsibility for the proper conduct of the trial.  However, the medical care given to, and medical decisions made on behalf of, subjects should  be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.  In terms of experience, the principal investigator should be well versed in the principals found in the International Conference on Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) as well as FDA regulations regarding clinical research.

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04 Oct What is clinical research or clinical trials and why would you want to participate?

Hello
My name is Jonathan Austin and I am a principal investigator at High Point Clinical Trials Center.  My background is in emergency medicine but I am now fully involved in clinical research here in High Point, North Carolina.

What is clinical research or clinical trials and why would you want to participate?

Clinical trials are part of and at the heart of all medical advances. Clinical trials look at new ways to prevent, detect, or treat disease. Treatments might be new drugs or new combinations of drugs, new surgical procedures or devices, or new ways to use existing treatments. The goal of a clinical trial is to determine if a new test or treatment works and is safe. Clinical trials can also look at other aspects of care, such as improving the quality of life for people with chronic illnesses.

The idea for a clinical research study — also known as a clinical trial — often originates in the laboratory. After researchers test new therapies or procedures in the laboratory and in animal studies, the most promising experimental treatments are moved into clinical trials, which are conducted in phases. During a trial, more information is gained about an experimental treatment, its risks, and its effectiveness.  A clinical study is led by a principal investigator like me.  My number one priority is the safety of our subjects and running a study takes many skill sets, but I aim to manage all studies with the highest ethical and quality standards.  Also, principal investigators lead the other members of the research team who regularly monitor the participants’ health to determine the study’s safety and effectiveness.
Being involved in clinical research allows me to have a greater awareness of cutting edge therapies and the ability to access new treatments or medial alternatives that may only be available through clinical trials..  Here at  High Point Clinical Trials Center, we all play a role in bringing potentially new treatments to the public  that may ultimately impact the healthcare of many patients in the future–it has been said that  today’s standard treatments were yesterday’s clinical trials.

People participate in clinical trials for a variety of reasons. Healthy volunteers say they participate to help others and to contribute to moving science forward. Participants with an illness or disease also participate to help others, but also to possibly receive the newest treatment and to have the additional care and attention from the clinical trial staff. Clinical trials offer hope for many people and an opportunity to help researchers find better treatments for others in the future.

Clinical research is medical research that involves people like you.  People volunteer to participate in carefully conducted investigations that ultimately uncover better ways to treat, prevent, diagnose, and understand human disease. Clinical research includes trials that test new treatments and therapies as well as long–term natural history studies, which provide valuable information about how disease and health progress.

Clinical research trials are a key component of the the drug development process.  More than 1400 medications and therapies have been approved through this process that helps treat or prevent serious disease or illness.  The importance of subject participation cannot be understated and will make a difference in the lives of many.  There is some personal satisfaction in knowing that I can offer this to the pubic as well, and it’s encouraging to know that we are increasing the community’s options for new treatments by bringing state of the art science to where we live (here in the Triad).

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