Regulation of Endogenous Glucose Production by Central KATP Channels

NCT03540758 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2018-9039R01DK069861
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes Mellitus; Glucose Metabolism Disorders

Keywords

Central KATP Channels; diabetes; diazoxide; endogenous glucose production

Outcome Measures

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.

  7 hour infusions, 4 days in total, separated at least 1 month apart, up to 1 year duration

Study Arms (4)

Non-diabetic (Diazoxide)

EXPERIMENTAL

Pancreatic clamp study will be done after giving Diazoxide (Proglycem) oral suspension to non-diabetic participants.

Drug: Diazoxide

Non-diabetic (Placebo)

PLACEBO COMPARATOR

Pancreatic clamp study will be done after giving a taste-matched placebo for Diazoxide (Proglycem) to non-diabetic participants.

Drug: Placebo

Non-diabetic (Diazoxide + Nicotinic Acid)

EXPERIMENTAL

Pancreatic clamp study will be done after giving Diazoxide (Proglycem) oral suspension to non-diabetic participants after lowering free fatty acids with a nicotinic acid (Niacin) infusion

Drug: Diazoxide; Drug: Nicotinic acid

Non-diabetic (Nicotinic Acid + placebo for diazoxide)

EXPERIMENTAL

Pancreatic clamp study will be done after lowering free fatty acids with a nicotinic acid (Niacin) infusion in non-diabetic participants, and after giving a taste-matched placebo for Diazoxide (Proglycem) toon-diabetic participants.

Drug: Nicotinic acid; Drug: Placebo

Interventions

Diazoxide DRUG

Non-diabetic participants will receive diazoxide at a dose of 4-7 mg/kg (based upon weight) during the pancreatic clamp study.

Also known as: Proglycem

Non-diabetic (Diazoxide + Nicotinic Acid); Non-diabetic (Diazoxide)

Nicotinic acid DRUG

Non-diabetic participants will receive nicotinic acid infusion based on weight (0.01 mg/kg/min) during the pancreatic clamp study.

Also known as: Niacin

Non-diabetic (Diazoxide + Nicotinic Acid); Non-diabetic (Nicotinic Acid + placebo for diazoxide)

Placebo DRUG

Non-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.

Also known as: Control

Non-diabetic (Nicotinic Acid + placebo for diazoxide); Non-diabetic (Placebo)

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For healthy (non-diabetic) participants:
• Age: 21-70 years old
• Body Mass Index (BMI) under 40 kg/m\^2
• Negative drug screen (see below)
• Normal Hemoglobin A1c (HbA1c) and fasting glucose
• Not participating in any other research study besides those done by the study team
• For T2D participants:
• Age: 21-70 years old
• BMI under 40 kg/m\^2
• Stable and moderate-to-poor glycemic control (HbA1c: 8.0-12.0%)
• Negative drug screen (see below)
• Not suffering from a previously diagnosed proliferative retinopathy, significant diabetic renal disease (urinary microalbumin \<100 μg/dl) or severe peripheral neuropathy (including cardiovascular and gastrointestinal autonomic neuropathy) per medical history

You may not qualify if:

• Age: Under 21 or over 70 years old
• BMI: \>40 kg/m\^2 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
• Urine microalbumin: \>300 mg/g of creatinine (in subjects with T2D)
• Uncontrolled hyperlipidemia defined as Triglycerides (TG) \> 400 mg/dL and/or Total Cholesterol \>300 mg/dL
• Clinically significant liver dysfunction including thrombocytopenia (platelets \<100,000/uL), anemia (as below), hypoalbuminemia (\<3.5 g/dL), coagulopathy (INR \> 1.5), and/or liver enzymes more than 3 times the upper limit of normal
• Clinically significant kidney dysfunction, Glomerular Filtration Rate (GFR): \<60 mg/dL
• Clinically significant anemia. Prospective subjects with hemoglobin below the lower limit of 12 g/dl for for men and 11 g/dL for women will be assessed with history and physical exam to rule out clinically significant anemia, defined as an individual with symptoms (e.g., fatigue, weakness, shortness of breath, palpitations), signs (pallor, brittle nails etc.), or currently under treatment for anemia. In the absence of a documented hemoglobin decrease or iron deficiency, subjects will not be excluded
• Clinically significant leukocytosis or leukopenia
• Clinically significant thrombocytopenia or thrombocytosis
• Coagulopathy
• Urinalysis: Clinically significant abnormalities
• Clinically significant electrolyte abnormalities
• Smoking \>10 cigarettes/day

Sponsors & Collaborators

• National Institutes of Health (NIH): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Albert Einstein College of Medicine: lead
• American Diabetes Association: collaborator
• Rutgers University: collaborator
• Vanderbilt University Medical Center: collaborator

Study Sites (1)

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

RECRUITING

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MeSH Terms

Conditions

Diabetes Mellitus; Glucose Metabolism Disorders

Interventions

Diazoxide; Niacin

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Meredith Hawkins, M.D., M.S.

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meredith Hawkins, M.D., M.S.

CONTACT

718-430-2903; meredith.hawkins@einsteinmed.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The subject will be blinded as to the intervention being received first (Drug or Placebo).
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2018
• First Posted: May 30, 2018
• Study Start: August 1, 2018
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Following publication

Locations

US (1)