Diabetes Mellitus, Type 2Phase 2NCT03685773
The Role of Hepatic Denervation in the Dysregulation of Glucose Metabolism in Liver Transplant Recipients
A Phase 2 study testing Diazoxide and Nicotinic acid in people with Diabetes Mellitus, Type 2 and Glucose, High Blood, run by Albert Einstein College of Medicine at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 21 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2, Glucose, High Blood, Glucose Metabolism Disorders
- What is being tested?
- Diazoxide and Nicotinic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Apr 2019to 21 Apr 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Liver Transplant at least one year ago
- Age: 21-70
Who cannot join
- 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.
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Albert Einstein College of Medicine
The Bronx, New York, 10461
About this study
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).
Read the detailed 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.
- Being tested
- Diazoxide, Placebo (for diazoxide), Nicotinic acid
- Keywords
- diabetes, type 2 diabetes, diazoxide, insulin resistance, MRI, liver transplant
- Medical subject headings
- Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DiazoxideDrug
Also called Proglycem
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)Drug
Also called Placebo
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 acidDrug
Also called Niacin
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.
| Study group | Role | What they receive |
|---|---|---|
| MRI: Non-diabetic transplant (Diazoxide) | Experimental | Diazoxide (up to 7 mg/kg) Receives: Drug: Diazoxide |
| MRI: Non-diabetic transplant (Placebo) | Placebo comparator | Taste-matched placebo for diazoxide Receives: Drug: Placebo (for diazoxide) |
| MRI: T2D transplant (Diazoxide) | Experimental | Diazoxide (up to 7 mg/kg) Receives: Drug: Diazoxide |
| MRI: T2D transplant (Placebo) | Placebo comparator | Taste-matched placebo for diazoxide Receives: Drug: Placebo (for diazoxide) |
| Clamp: Non-diabetic transplant (Diazoxide) | Experimental | Diazoxide (up to 7 mg/kg) before pancreatic clamp study Receives: Drug: Diazoxide |
| Clamp: Non-diabetic transplant (Placebo) | Placebo comparator | Taste-matched placebo (for diazoxide) before pancreatic clamp study Receives: Drug: Placebo (for diazoxide) |
| Clamp: T2D transplant (Diazoxide) | Experimental | Diazoxide (up to 7 mg/kg) before pancreatic clamp study Receives: Drug: Diazoxide |
| Clamp: T2D transplant (Placebo) | Placebo comparator | Taste-matched placebo (for diazoxide) before pancreatic clamp study Receives: Drug: Placebo (for diazoxide) |
| Clamp: T2D transplant (Diazoxide + Nicotinic Acid) | Experimental | Nicotinic acid infusion and diazoxide (up to 7 mg/kg) before pancreatic clamp study Receives: Drug: Diazoxide; Drug: Nicotinic acid |
| Clamp: T2D transplant (Placebo + Nicotinic Acid) | Experimental | Nicotinic acid infusion and placebo (for diazoxide) before pancreatic clamp study Receives: Drug: Placebo (for diazoxide); Drug: Nicotinic acid |
| MRI: T2D transplant (Diazoxide + Nicotinic Acid) | Experimental | Nicotinic acid infusion and diazoxide (up to 7 mg/kg) Receives: Drug: Diazoxide; Drug: Nicotinic acid |
| MRI: T2D transplant (Placebo + Nicotinic Acid) | Experimental | Nicotinic acid infusion and placebo (for diazoxide) Receives: Drug: Placebo (for diazoxide); Drug: Nicotinic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7-7.5 hours
Secondary outcomes (1)
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.
Measured: Baseline, 2 hours post dosing, 4 hours post dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2018
- Study start21 Apr 2019
- Primary completion21 Apr 2023
- Study completion21 Apr 2023
Why it stopped: Permanently terminated due to COVID-19 given the poor vaccine penetrance in liver transplant recipients. This is not a suspension of IRB approval.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Albert Einstein College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Meredith Hawkins, M.D., M.S., Principal investigator, Albert Einstein College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03685773
- Sponsor's protocol ID
- 2018-9506
- Status last verified
- Jun 2023
- First submitted
- 24 Sep 2018
- Last updated
- 5 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Hepatic Denervation in the Dysregulation of Glucose Metabolism in Liver Transplant Recipients
- ClinicalTrials.gov ID
- NCT03685773
- Acronym / sponsor ID
- 2018-9506
- Keywords
- diabetes, type 2 diabetes, diazoxide, insulin resistance, MRI, liver transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Permanently terminated due to COVID-19 given the poor vaccine penetrance in liver transplant recipients. This is not a suspension of IRB approval.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Albert Einstein College of MedicineUniversity, hospital or other
- Study start
- 21 Apr 2019 (actual)
- Primary completion
- 21 Apr 2023 (actual)
- Study completion
- 21 Apr 2023 (actual)
- First posted
- 26 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| MRI: Non-diabetic transplant (Diazoxide) | Experimental | Drug: DiazoxideDiazoxide (up to 7 mg/kg) |
| MRI: Non-diabetic transplant (Placebo) | Placebo comparator | Drug: Placebo (for diazoxide)Taste-matched placebo for diazoxide |
| MRI: T2D transplant (Diazoxide) | Experimental | Drug: DiazoxideDiazoxide (up to 7 mg/kg) |
| MRI: T2D transplant (Placebo) | Placebo comparator | Drug: Placebo (for diazoxide)Taste-matched placebo for diazoxide |
| Clamp: Non-diabetic transplant (Diazoxide) | Experimental | Drug: DiazoxideDiazoxide (up to 7 mg/kg) before pancreatic clamp study |
| Clamp: Non-diabetic transplant (Placebo) | Placebo comparator | Drug: Placebo (for diazoxide)Taste-matched placebo (for diazoxide) before pancreatic clamp study |
| Clamp: T2D transplant (Diazoxide) | Experimental | Drug: DiazoxideDiazoxide (up to 7 mg/kg) before pancreatic clamp study |
| Clamp: T2D transplant (Placebo) | Placebo comparator | Drug: Placebo (for diazoxide)Taste-matched placebo (for diazoxide) before pancreatic clamp study |
| Clamp: T2D transplant (Diazoxide + Nicotinic Acid) | Experimental | Drug: Diazoxide, Drug: Nicotinic acidNicotinic acid infusion and diazoxide (up to 7 mg/kg) before pancreatic clamp study |
| Clamp: T2D transplant (Placebo + Nicotinic Acid) | Experimental | Drug: Placebo (for diazoxide), Drug: Nicotinic acidNicotinic acid infusion and placebo (for diazoxide) before pancreatic clamp study |
| MRI: T2D transplant (Diazoxide + Nicotinic Acid) | Experimental | Drug: Diazoxide, Drug: Nicotinic acidNicotinic acid infusion and diazoxide (up to 7 mg/kg) |
| MRI: T2D transplant (Placebo + Nicotinic Acid) | Experimental | Drug: Placebo (for diazoxide), Drug: Nicotinic acidNicotinic acid infusion and placebo (for diazoxide) |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Liver Transplant at least one year ago
- Age: 21-70
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DiazoxideAlso: ProglycemMRI 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. | Drug | Clamp: Non-diabetic transplant (Diazoxide), Clamp: T2D transplant (Diazoxide + Nicotinic Acid), Clamp: T2D transplant (Diazoxide), MRI: Non-diabetic transplant (Diazoxide), MRI: T2D transplant (Diazoxide + Nicotinic Acid), MRI: T2D transplant (Diazoxide) |
| Placebo (for diazoxide)Also: PlaceboMRI 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. | Drug | Clamp: Non-diabetic transplant (Placebo), Clamp: T2D transplant (Placebo + Nicotinic Acid), Clamp: T2D transplant (Placebo), MRI: Non-diabetic transplant (Placebo), MRI: T2D transplant (Placebo + Nicotinic Acid), MRI: T2D transplant (Placebo) |
| Nicotinic acidAlso: NiacinType 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. | Drug | Clamp: T2D transplant (Diazoxide + Nicotinic Acid), Clamp: T2D transplant (Placebo + Nicotinic Acid), MRI: T2D transplant (Diazoxide + Nicotinic Acid), MRI: T2D transplant (Placebo + Nicotinic Acid) |
Primary outcome
Endogenous glucose production (EGP)
Time frame: 7-7.5 hours
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.
1 secondary outcome
Change in Arterial Spin Labeling (ASL) signal
Time frame: Baseline, 2 hours post dosing, 4 hours post dosing
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Meredith Hawkins, M.D., M.S. principal investigator
Albert Einstein College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Diazoxide and Nicotinic acid in people with Diabetes Mellitus, Type 2 and Glucose, High Blood, run by Albert Einstein College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 5 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endogenous glucose production (EGP) (time frame: 7-7.5 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2023; AzTrials last refreshed its copy on 8 Nov 2026.