Clinical Trials Logo

Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT03685773
Other study ID # 2018-9506
Secondary ID
Status Withdrawn
Phase Phase 2
First received
Last updated
Start date April 21, 2019
Est. completion date April 21, 2023

Study information

Verified date June 2023
Source Albert Einstein College of Medicine
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

It is believed that important brain centers send signals through the vagus nerve to the liver to suppress the amount of glucose (sugar) that gets produced. People who have received liver transplants have had their vagus nerve cut during transplantation, and many of these individuals have diabetes at one year post-transplant. The goals of this study are: to see whether metabolic control centers in the brain can still be activated normally with the medication diazoxide in patients who have had a liver transplant, and to understand whether disrupting the vagus nerve would result in excess glucose being produced by the liver (ie. a potential mechanism for why these patients develop diabetes).


Description:

In this study, investigators will study both diabetic and non-diabetic individuals who are otherwise healthy more than one year after receiving a liver transplant. They will participate in at least one of the following two parts of this study: The first involves functional magnetic resonance imaging (fMRI), and the second is using a day-long infusion study called a "pancreatic clamp." Functional magnetic resonance imaging (fMRI) is a technique for measuring and mapping brain activity that is noninvasive and safe. This technique relies on the fact that blood flow in the brain and the activity of brain cells are coupled. Investigators will observe the activity of metabolically-relevant areas of the brain by activating potassium channels with diazoxide at baseline and at 2-hour intervals vs when given placebo. In the pancreatic clamp study, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of sugar in the blood) are infused with an intravenous catheter. Blood samples are collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body which are related to glucose metabolism. The rates of endogenous glucose production (a measure of the body's production of sugar) will be measured as the main measurement of the study. All participants will be screened prior to study enrollment. For the fMRI studies, eligible participants will come on two separate occasions for day-long study visits (one day in which the brain will be imaged before and after receiving diazoxide (a potassium channel activator), and one day in which the brain will be imaged before and after placebo. For the pancreatic clamp studies, eligible participants will come on two separate occasions for day-long study visits (one study with diazoxide, and one study with placebo). All studies in participants with type 2 diabetes will include overnight admissions prior to the study day for gradual normalizing of blood glucose through the infusion of insulin. Participants without diabetes will not have to stay for an overnight admission. Study participants with type 2 diabetes will also be eligible for an additional study in which Nicotinic Acid will be infused overnight to lower free fatty acid (FFA) levels. It will be determined whether FFA lowering will impact the fMRI studies and clamp studies that will be performed the next day.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date April 21, 2023
Est. primary completion date April 21, 2023
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 21 Years to 70 Years
Eligibility Inclusion Criteria: - Liver Transplant at least one year ago - Age: 21-70 Exclusion Criteria: - BP > 150/90 or <90/60 on more than one occasion, unless there is a documented history of white coat hypertension by treating physician. - Triglycerides > 400 mg/dl and/or Total Cholesterol >300 mg/dl - Clinically significant liver dysfunction - Clinically significant kidney dysfunction, GFR: <60 mg/dL - Anemia: HgB <12.5 for men and <11.0 for women - Positive urine drug test. Occasional use of cannabis (once or twice per week) will not be a basis for exclusion. - Urinalysis: Clinically significant abnormalities - Clinically significant electrolyte abnormalities - Smoking >10 cig/day - Alcohol: Men >14 drinks/wk or >4 drinks/day, Women >7 drinks/wk or >3 drinks/day - History of 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 T4 and TSH will be checked) - Pregnant women - Subject enrolled in another study less than one month prior to the anticipated start date in the proposed study, besides those done by our group - Family history: 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

Study Design


Intervention

Drug:
Diazoxide
MRI studies: Non-diabetic and T2D participants will receive diazoxide (up to 7 mg/kg) between baseline MRI scan and second MRI scan. Clamp studies: Non-diabetic participants will not require an overnight admission. They will receive diazoxide (up to 7 mg/kg) and undergo the pancreatic clamp study. Type 2 diabetic participants will be admitted the evening before the study day to normalize blood sugar levels. They will then receive diazoxide (up to 7 mg/kg) the next morning and undergo the pancreatic clamp study.
Placebo (for diazoxide)
MRI studies: Non-diabetic and T2D participants will receive placebo (for diazoxide) between baseline MRI scan and second MRI scan. Clamp studies: Non-diabetic participants will not require an overnight admission. They will receive a taste-matched placebo (for diazoxide) and undergo the pancreatic clamp study. Type 2 diabetic participants will be admitted the evening before the study day to normalize blood sugar levels. They will then receive a taste-matched placebo (for diazoxide) the next morning and undergo the pancreatic clamp study.
Nicotinic acid
Type 2 diabetic participants in this arm will receive a nicotinic acid infusion to lower free fatty acid levels. They will then receive diazoxide (up to 7 mg/kg) the next morning and undergo the MRI or pancreatic clamp study.

Locations

Country Name City State
United States Albert Einstein College of Medicine Bronx New York

Sponsors (1)

Lead Sponsor Collaborator
Albert Einstein College of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Endogenous glucose production (EGP) Rates of EGP (a measure of the body's production of sugar) will be measured during pancreatic clamp studies, with suppression of pancreatic hormones by somatostatin infusion and basal hormone replacement. 7-7.5 hours
Secondary Change in Arterial Spin Labeling (ASL) signal Change in Arterial Spin Labeling (ASL) signal measured using 3T MRI from baseline to 2 hours post dosing, and 2 hours post dosing to 4 hours post dosing. ASL is a measure of brain blood flow, and an increase in ASL is interpreted as an increase in brain activity. Data is collected at three time points during each of the two visits (pre dosing, 2 hours post dosing, 4 hours post dosing). Response to diazoxide is compared between 3 time points for each group, and this response is then compared between non-diabetic and type 2 diabetic liver transplant subjects. Baseline, 2 hours post dosing, 4 hours post dosing
See also
  Status Clinical Trial Phase
Active, not recruiting NCT05666479 - CGM Monitoring in T2DM Patients Undergoing Orthopaedic Replacement Surgery
Completed NCT05647083 - The Effect of Massage on Diabetic Parameters N/A
Active, not recruiting NCT05661799 - Persistence of Physical Activity in People With Type 2 Diabetes Over Time. N/A
Completed NCT03686722 - Effect of Co-administration of Metformin and Daclatasvir on the Pharmacokinetis and Pharmacodynamics of Metformin Phase 1
Completed NCT02836704 - Comparison of Standard vs Higher Starting Dose of Insulin Glargine in Chinese Patients With Type 2 Diabetes (Glargine Starting Dose) Phase 4
Completed NCT01819129 - Efficacy and Safety of FIAsp Compared to Insulin Aspart in Combination With Insulin Glargine and Metformin in Adults With Type 2 Diabetes Phase 3
Completed NCT04562714 - Impact of Flash Glucose Monitoring in People With Type 2 Diabetes Using Non-Insulin Antihyperglycemic Therapy N/A
Completed NCT02009488 - Treatment Differences Between Canagliflozin and Placebo in Insulin Secretion in Subjects With Type 2 Diabetes Mellitus (T2DM) Phase 1
Completed NCT05896319 - Hyaluronic Acid Treatment of the Post-extraction Tooth Socket Healing in Subjects With Diabetes Mellitus Type 2 N/A
Recruiting NCT05598203 - Effect of Nutrition Education Groups in the Treatment of Patients With Type 2 Diabetes N/A
Completed NCT05046873 - A Research Study Looking Into Blood Levels of Semaglutide and NNC0480-0389 When Given in the Same Injection or in Two Separate Injections in Healthy People Phase 1
Completed NCT04030091 - Pulsatile Insulin Infusion Therapy in Patients With Type 1 and Type 2 Diabetes Mellitus Phase 4
Terminated NCT04090242 - Impact of App Based Diabetes Training Program in Conjunction With the BD Nano Pen Needle in People With T2 Diabetes N/A
Completed NCT03620357 - Continuous Glucose Monitoring & Management In Type 2 Diabetes (T2D) N/A
Completed NCT03604224 - A Study to Observe Clinical Effectiveness of Canagliflozin 300 mg Containing Treatment Regimens in Indian Type 2 Diabetes Participants With BMI>25 kg/m^2, in Real World Clinical Setting
Completed NCT01696266 - An International Survey on Hypoglycaemia Among Insulin-treated Patients With Diabetes
Completed NCT03620890 - Detemir Versus NPH for Type 2 Diabetes Mellitus in Pregnancy Phase 4
Withdrawn NCT05473286 - A Research Study Looking at How Oral Semaglutide Works in People With Type 2 Diabetes in Germany, as Part of Local Clinical Practice
Not yet recruiting NCT05029804 - Effect of Walking Exercise Training on Adherence to Disease Management and Metabolic Control in Diabetes N/A
Completed NCT04531631 - Effects of Dorzagliatin on 1st Phase Insulin and Beta-cell Glucose Sensitivity in T2D and Monogenic Diabetes Phase 2