Investigating how brain medication affects liver sugar production in diabetes

Regulation of Endogenous Glucose Production by Central KATP Channels

This study is testing whether a brain medication can change how the liver produces sugar in people with type 2 diabetes and healthy individuals.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 21 Years to 70 Years
• Sex: All
• Sponsor: Albert Einstein College of Medicine (other)
• Locations: 1 site (The Bronx, New York)
• Trial ID: NCT03540758 on ClinicalTrials.gov

What this trial studies

This study aims to explore the role of the central nervous system in regulating glucose production by the liver in individuals with type 2 diabetes. Participants will undergo a pancreatic clamp procedure where glucose and insulin will be infused, and blood samples will be collected to measure glucose levels and related hormones. The study will compare the effects of diazoxide, a medication that activates potassium channels in the brain, against a placebo to determine its impact on endogenous glucose production. Both healthy individuals and those with type 2 diabetes will be included in the study to assess the medication's effects across different populations.

Who should consider this trial

Good fit: Ideal candidates include adults aged 21-70 with type 2 diabetes who have moderate-to-poor glycemic control or healthy individuals without diabetes.

Not a fit: Patients with severe diabetes complications or those outside the age and BMI criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new treatments that better control blood sugar levels in patients with type 2 diabetes.

How similar studies have performed: Previous studies have shown promise in understanding brain-liver signaling in glucose metabolism, but this specific approach using diazoxide is novel.

Eligibility criteria

Inclusion Criteria:

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
* In general good health (see below for exclusions)
* 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
* Diabetic subjects will be otherwise in good health (see below for exclusions), taking no medications that might affect study eligibility based on review by study doctor, and not participating in any other research study besides those done by the study team

Exclusion Criteria:

* 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
* Urine drug screen positive for any of the following: amphetamines, barbiturates, benzodiazepines, cocaine, methadone, opiates, oxycodone, phencyclidine (PCP). Amphetamines, oxycodone, opiates, methadone, and benzodiazepines have been shown to affect glucose metabolism (increased glycemia, increased fasting insulin levels, delayed insulin response to food ingestion, insulin deficiency). As the drug test available in the Clinical Research Center (CRC) is a 7-drug panel, the investigator team cannot specifically choose which drugs are screened for. Additionally, in the interest of selecting patients on the basis of their reliability and dependability, the investigator team would like to exclude participants using illicit drugs. Occasional use of cannabis (once or twice per week) is not an exclusion factor. If the test is read as "indeterminate" it will be repeated at the bedside and an additional sample will be sent to the lab. Decision to enroll subject that day prior to results from lab being available will be decided on a case-by-case basis, i.e., when all previous drug testing had been negative and clinical suspicion is very low
* Urinalysis: Clinically significant abnormalities
* Clinically significant electrolyte abnormalities
* Smoking \>10 cigarettes/day
* Alcohol: Men \>14 drinks/week or \>4 drinks/day, Women \>7 drinks/week or \>3 drinks/day
* History of chronic liver disease, active hepatitis infection, HIV/AIDS, chronic kidney disease (stage 3 or greater), active cancer, cardiovascular disease or other heart disease, systemic rheumatologic conditions, seizures, bleeding disorders, muscle disease
* Surgeries that involve removal of endocrine glands except for thyroidectomy (if euthyroid on thyroid hormone replacement - if such history free thyroxine (fT4) and Thyroid Stimulating Hormone (TSH) will be checked)
* Pregnant women
* Subject enrolled in another study less than one month prior to the anticipated start date of the proposed study, besides those done by our group
* Family history of premature cardiac death
* Allergies to medication administered during study
* Uncontrolled psychiatric disorders
* Any condition which in the opinion of the PI makes the subject ill suited for participation in the study

Where this trial is running

The Bronx, New York

• Albert Einstein College of Medicine — The Bronx, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Meredith Hawkins, M.D., M.S. — Albert Einstein College of Medicine
• Study coordinator: Meredith Hawkins, M.D., M.S.

Conditions: Diabetes Mellitus, Glucose Metabolism Disorders, Central KATP Channels, diabetes, diazoxide, endogenous glucose production