Regulation of Endogenous Glucose Production by Central KATP Channels
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age21-70
SponsorAlbert Einstein College of Medicine
About this trial
Type 2 diabetes (T2D) affects the ability of the body to process glucose (sugar). Under fasting conditions, the liver is able to make sugar to maintain glucose levels in an important process called endogenous glucose production (EGP). Previous studies suggest that the central nervous system (CNS), including the brain, helps to regulate levels of glucose in the body by communicating with the liver. This process can be impaired in people with type 2 diabetes, and can contribute to the high level of glucose seen in these individuals.
The purpose of this study is to understand how activating control centers of the brain with a medication called diazoxide can affect how much glucose (sugar) is made by the liver. This is particularly important for people with diabetes who have very high production of glucose, which in turn can lead to diabetes complications.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Age: 21-70 years old
Body Mass Index (BMI) under 40 kg/m²
Negative drug screen (see below)
Normal Hemoglobin A1c (HbA1c) and fasting glucose
Disqualifiers
Age: Under 21 or over 70 years old
BMI: >40 kg/m² for Type 2 Diabetes (T2D) and Non-Diabetic (ND) subjects
Blood pressure >150/90 or <90/60 on more than one occasion
Severe polydipsia and polyuria (in subjects with T2D). Since polydipsia and polyuria are common symptoms of T2D, the distinction "severe" denotes that the subject indicates a worsening in the symptoms and/or an experience of discomfort related to the symptoms at the time of screening and/or at the time of withdrawal from the medications
Trial design
Design model
Crossover
Treatments tested in this trial
Diazoxide
DrugNon-diabetic participants will receive diazoxide at a dose of 4-7 mg/kg (based upon weight) during the pancreatic clamp study.
Nicotinic acid
DrugNon-diabetic participants will receive nicotinic acid infusion based on weight (0.01 mg/kg/min) during the pancreatic clamp study.
Placebo
DrugNon-diabetic participants will receive placebo and undergo the pancreatic clamp study. T2D participants will have their blood sugar levels normalized, and will then receive a taste-matched placebo for diazoxide before undergoing the pancreatic clamp study.
Treatment groups
100 Participants
are divided into 4 treatment groupsGroup A: Non-diabetic (Diazoxide)Experimental treatment 1 intervention
Group B: Non-diabetic (Placebo)Placebo comparator 1 intervention
Group C: Non-diabetic (Diazoxide + Nicotinic Acid)Experimental treatment 2 interventions
Group D: Non-diabetic (Nicotinic Acid + placebo for diazoxide)Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Change in Endogenous glucose production (EGP) rate
Rates of EGP (a measure of the body's production of sugar) will be measured using analysis of blood samples taken throughout the pancreatic clamp procedure under various treatment conditions (e.g., placebo, diazoxide, nicotinic acid, nicotinic acid/diazoxide), by monitoring changes in the level of a non-radioactive, naturally occurring form of glucose (sugar). Measurement of blood glucose concentrations will either be performed with a Precision Xceed Pro glucometer or an Analox glucose analyzer in the study room. Increased EGP is the major cause of fasting hyperglycemia. EGP will be determined by subtracting the rates of glucose infusion from the tracer-derived Rates of glucose appearance (Ra). Rates of change in EGP will be reported in concentration/time and summarized by study arm using basic descriptive statistics.
Time frame
7 hour infusions, 4 days in total, separated at least 1 month apart, up to 1 year durationSponsors and contacts
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Albert Einstein College of Medicine
Lead sponsor
National Institutes of Health (NIH)
Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator
American Diabetes Association
Collaborator
Rutgers University
Collaborator
Vanderbilt University Medical Center
Collaborator
Source ClinicalTrials.gov