Use of Functional MRI to Assess Functional Hypothalamic Activation in Response to Diazoxide

NCT03566511 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2018-9040R01DK069861
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to determine whether metabolic control centers in the brain can be activated in patients with type 2 diabetes (T2D) as compared to non-diabetic individuals. This is important since people with diabetes have inappropriately high production of glucose, which could be at least in part due to impaired activation of important brain centers.

Conditions

Diabetes Mellitus, Type 2; Glucose, High Blood; Glucose Metabolism Disorders (Including Diabetes Mellitus)

Keywords

diabetes; type 2 diabetes; insulin resistance; diazoxide; MRI

Outcome Measures

Primary Outcomes (1)

• Change in Arterial Spin Labeling (ASL) Signal Measured Using 3T MRI From Baseline to 5 Hours Post Dosing

  Arterial Spin Labeling data was acquired and converted by the Gruss Magnetic Resonance Research Center (MRRC) and reported as Hypothalamic Cerebral Blood Flow (CBF) which is a more meaningful clinical endpoint measurement. Data was collected at three time points during each of the two study visits (pre dosing, 2 hours post dosing, and 5 hours post dosing). CBF values at the respective timepoints are summarized in mL/100g/min units and reported by study arm. An increase in CBF is correlated with an increase in brain activity.

  2 hours and 5 hours post dosing

Study Arms (4)

Healthy (Diazoxide)

EXPERIMENTAL

Proglycem, oral suspension (4-7 mg/kg). Healthy participants will receive diazoxide between MRI scans.

Drug: Diazoxide

Healthy (Placebo)

PLACEBO COMPARATOR

Taste-matched placebo. Healthy participants will receive placebo between MRI scans.

Drug: Placebo

T2D (Diazoxide)

EXPERIMENTAL

Proglycem, oral suspension (4-7 mg/kg). Type 2 diabetic (T2D) participants will receive diazoxide between MRI scans.

Drug: Diazoxide

T2D (Placebo)

PLACEBO COMPARATOR

Taste-matched placebo. T2D participants will receive placebo between MRI scans.

Drug: Placebo

Interventions

Diazoxide DRUG

Healthy and T2D participants will receive diazoxide at a dose of 4-7 mg/kg (based upon weight) between baseline MRI scan and second MRI scan.

Also known as: Proglycem

Healthy (Diazoxide); T2D (Diazoxide)

Placebo DRUG

Healthy and T2D participants will receive placebo between baseline MRI scan and second MRI scan.

Healthy (Placebo); T2D (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:

• Type 2 Diabetes (T2D)
• Age: Between 21 and 70 y.o.
• BMI: \<35
• A1c 8.0-12.0%
• Negative drug screen
• Not suffering from proliferative retinopathy, significant diabetic renal disease or severe neuropathy (including cardiovascular and gastrointestinal autonomic dysfunction)
• Healthy (ND)
• Age: Between 21 and 70 y.o.
• BMI: \<30
• Negative drug screen
• No family history of diabetes among first-degree relatives (mother, father)

You may not qualify if:

• Age: Under 21 or over 70 y.o.
• BMI: \>35 for T2D and \>30 for ND
• Hypertension
• Severe polydipsia and polyuria
• Uncontrolled hyperlipidemia
• Clinically significant liver dysfunction
• Clinically significant kidney dysfunction
• Anemia
• Clinically significant leukocytosis or leukopenia
• Clinically significant thrombocytopenia or thrombocytosis
• Coagulopathy
• Positive urine drug screen
• Urinalysis: Clinically significant abnormalities
• Clinically significant electrolyte abnormalities
• Smoking \>10 cig/day

Sponsors & Collaborators

• Meredith Hawkins: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• American Diabetes Association: collaborator

Study Sites (1)

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Diabetes Mellitus; Insulin Resistance

Interventions

Diazoxide

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Instrumentation got remodeled and further studies were unable to be conducted and the trial was unable to be completed as proposed.

Results Point of Contact

• Title: Dr. Meredith Hawkins
• Organization: Albert Einstein College of Medicine

meredith.hawkins@einsteinmed.edu

718-839-7975

Study Officials

• Meredith Hawkins, M.D., M.S.

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The subject will be blinded to which study drug is received first (Drug or Placebo).
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Study was initially intended to be a double blinded, randomized, crossover design; however, it was terminated early due to issues with magnetic resonance (MR) system.

Study Record Dates

• First Submitted: May 17, 2018
• First Posted: June 25, 2018
• Study Start: June 12, 2018
• Primary Completion: August 1, 2020
• Study Completion: August 1, 2020
• Last Updated: May 31, 2025
• Results First Posted: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)