Hyperinsulinemic HypoglycemiaPhase 1NCT02685852
Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia
A Phase 1 study testing Exenatide and Acarbose in people with Hyperinsulinemic Hypoglycemia, run by University of Minnesota at 1 site in United States.
Trial summary
The purpose of the study is to evaluate the effectiveness of exenatide in adults experiencing episodes of hyperinsulinemic hypoglycemia following Roux-en-Y bariatric surgery. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Hyperinsulinemic Hypoglycemia
- What is being tested?
- Exenatide and Acarbose
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2016to 22 Jul 2019
- Phase
- Phase 1
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- must have undergone RYGB and subsequently developed post-prandial hypoglycemia (defined as at least 3 episodes over a six-month period with documented capillary blood sugars [<60 mg/dL with hypoglycemic symptoms). Subjects may also have had a formal mixed meal tolerance test with post meal blood sugar <60 mg/dL.
- Subjects who otherwise meet the study criteria above with hypoglycemia symptoms but who do not have documented hypoglycemia by plasma measurement may undergo a screening visit to document the requisite levels for consideration into the study.
Who cannot join
- Chronic or acute diseases of the liver.
- Chronic or acute diseases of the pancreas (including type 1 diabetes or pancreatitis or a history of pancreatitis). Subjects may have a diagnosis of type 2 diabetes but must no longer require diabetes medication.
- Chronic or acute diseases of the kidneys.
- Known malignancies and must not have a family history of medullary thyroid cancer.
- History of pre-RYGB hypoglycemia symptoms or low documented plasma glucose preoperatively.
- Pregnant or plans to become pregnant throughout study duration
- Breastfeeding
- Medication exclusions in addition to the current use of diabetes medications. Subjects will be excluded if they have previously taken GLP-1 agonists.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota Medical Center
Minneapolis, Minnesota, 55455
About this study
Official title: A Pilot Study Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia Post-RYGB
The purpose of the study is to evaluate the effectiveness of exenatide in adults experiencing episodes of hyperinsulinemic hypoglycemia following Roux-en-Y bariatric surgery.
Read the detailed description
Roux-en-Y gastric bypass surgery (RYGB) is one of the most common bariatric surgeries in the United States and is generally highly effective for weight loss. Unfortunately, among the potential complications is hyperinsulinemic hypoglycemia. Though the prevalence of this disorder has not been fully characterized, it can be associated with debilitating symptoms which severely impact quality of life and can be life-threatening. The underlying pathophysiology of hyperinsulinemic hypoglycemia likely involves a mismatch in the amount of insulin secreted in response to mealtime carbohydrate absorption. It has been observed that the ingestion of a high carbohydrate load often leads to a modest rise in post-prandial glucose levels followed by an inappropriately exaggerated insulin release among individuals with this condition. Low carbohydrate diet sometimes provides full or partial relief of the symptoms.
Standard medical management for RYGB associated postprandial hyperinsulinemic hypoglycemia includes acarbose, which partially reduces carbohydrate absorption from the gut, and diazoxide, which directly inhibits insulin release from pancreatic beta cells. However, the medical options are not reliably effective, leading some individuals to reverse RYGB, which also may not be effective, or even undergo partial pancreatectomy, risking additional complications such as diabetes. Much more reliably effective treatments are needed for this special population who develop this bariatric surgical complication.
Potential mechanisms contributing to the mismatched insulin secretion post RYGB include decreased systemic and adipose tissue inflammation, and increased insulin receptor expression in liver and skeletal muscle, and increases in adiponectin.
- Conditions
- Hyperinsulinemic Hypoglycemia
- Being tested
- Exenatide, Acarbose, Exenatide Placebo, Acarbose Placebo
- Medical subject headings
- Congenital Hyperinsulinism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExenatideDrug
Also called Byetta
Exenatide at a dose of 5 mcg
AcarboseDrug
Acarbose at a dose of 25 mg
Exenatide PlaceboDrug
Placebo for Exenatide
Acarbose PlaceboDrug
Placebo for Acarbose
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Exenatide (5mcg) + Acarbose Placebo | Active comparator | Exenatide (5 mcg) 30 minutes before the high-carb meal is delivered and acarbose placebo immediately prior to the high-carb meal Receives: Drug: Exenatide; Drug: Acarbose Placebo |
| Arm 2: Exenatide (5mcg) + Acarbose (25mg) | Active comparator | Exenatide (5 mcg) 30 minutes before the high-carb meal is delivered and acarbose (25 mg) immediately prior to the high-carb meal Receives: Drug: Exenatide; Drug: Acarbose |
| Arm 3: Exenatide Placebo + Acarbose (25mg) | Placebo comparator | Exenatide placebo 30 minutes before the high-carb meal is delivered and acarbose (25 mg) immediately prior to the high-carb meal Receives: Drug: Acarbose; Drug: Exenatide Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucose area under the curve (AUC) following treatment for each 4-hour test period
Each time point (15, 30, 45, 60, 90, 120, 180 and 240 minutes) will be used to calculate AUC using the trapezoidal method.
Measured: During the 4-hour test period
Presence of hypoglycemia
If at each time-point (15, 30, 45, 60, 90, 120, 180 and 240 minutes) plasma glucose is <60 mg/dL, participants will be defined as hypoglycemic
Measured: 15, 30, 45, 60, 90, 120, 180 and 240 minutes
Secondary outcomes (3)
Minimum post-prandial blood sugar level (mg/dL)
The lowest post-prandial blood glucose level at any time point (15, 30, 45, 60, 90, 120, 180 and 240 minutes) may be used as the minimum post-prandial blood sugar level (mg/dL).
Measured: post meal test
Change in post-prandial blood glucose from 0min to 120min
% change in blood glucose 0min to 120min
Measured: 0min to 120min
Change in post-prandial Insulin levels (mcg/mL)
% change in insulin 0min to 120min
Measured: 0min to 120min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2016 (estimated)
- Study startFeb 2016
- Primary completion22 Jul 2019
- Study completion22 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hyperinsulinemic HypoglycemiaStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shalamar D Sibley, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02685852
- Sponsor's protocol ID
- 1503M65841
- Status last verified
- Apr 2021
- First submitted
- 19 Jan 2016
- Last updated
- 6 May 2021
- 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 6 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia Post-RYGB
- ClinicalTrials.gov ID
- NCT02685852
- Acronym / sponsor ID
- 1503M65841
- Conditions
- Hyperinsulinemic Hypoglycemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- Feb 2016
- Primary completion
- 22 Jul 2019 (actual)
- Study completion
- 22 Jul 2019 (actual)
- First posted
- 19 Feb 2016 (estimated)
- 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.
The purpose of the study is to evaluate the effectiveness of exenatide in adults experiencing episodes of hyperinsulinemic hypoglycemia following Roux-en-Y bariatric surgery.
Detailed description
Roux-en-Y gastric bypass surgery (RYGB) is one of the most common bariatric surgeries in the United States and is generally highly effective for weight loss. Unfortunately, among the potential complications is hyperinsulinemic hypoglycemia. Though the prevalence of this disorder has not been fully characterized, it can be associated with debilitating symptoms which severely impact quality of life and can be life-threatening. The underlying pathophysiology of hyperinsulinemic hypoglycemia likely involves a mismatch in the amount of insulin secreted in response to mealtime carbohydrate absorption. It has been observed that the ingestion of a high carbohydrate load often leads to a modest rise in post-prandial glucose levels followed by an inappropriately exaggerated insulin release among individuals with this condition. Low carbohydrate diet sometimes provides full or partial relief of the symptoms.
Standard medical management for RYGB associated postprandial hyperinsulinemic hypoglycemia includes acarbose, which partially reduces carbohydrate absorption from the gut, and diazoxide, which directly inhibits insulin release from pancreatic beta cells. However, the medical options are not reliably effective, leading some individuals to reverse RYGB, which also may not be effective, or even undergo partial pancreatectomy, risking additional complications such as diabetes. Much more reliably effective treatments are needed for this special population who develop this bariatric surgical complication.
Potential mechanisms contributing to the mismatched insulin secretion post RYGB include decreased systemic and adipose tissue inflammation, and increased insulin receptor expression in liver and skeletal muscle, and increases in adiponectin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Exenatide (5mcg) + Acarbose Placebo | Active comparator | Drug: Exenatide, Drug: Acarbose PlaceboExenatide (5 mcg) 30 minutes before the high-carb meal is delivered and acarbose placebo immediately prior to the high-carb meal |
| Arm 2: Exenatide (5mcg) + Acarbose (25mg) | Active comparator | Drug: Exenatide, Drug: AcarboseExenatide (5 mcg) 30 minutes before the high-carb meal is delivered and acarbose (25 mg) immediately prior to the high-carb meal |
| Arm 3: Exenatide Placebo + Acarbose (25mg) | Placebo comparator | Drug: Acarbose, Drug: Exenatide PlaceboExenatide placebo 30 minutes before the high-carb meal is delivered and acarbose (25 mg) immediately prior to the high-carb meal |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- must have undergone RYGB and subsequently developed post-prandial hypoglycemia (defined as at least 3 episodes over a six-month period with documented capillary blood sugars [<60 mg/dL with hypoglycemic symptoms). Subjects may also have had a formal mixed meal tolerance test with post meal blood sugar <60 mg/dL.
- Subjects who otherwise meet the study criteria above with hypoglycemia symptoms but who do not have documented hypoglycemia by plasma measurement may undergo a screening visit to document the requisite levels for consideration into the study.
Key exclusion criteria (8 listed)
- Chronic or acute diseases of the liver.
- Chronic or acute diseases of the pancreas (including type 1 diabetes or pancreatitis or a history of pancreatitis). Subjects may have a diagnosis of type 2 diabetes but must no longer require diabetes medication.
- Chronic or acute diseases of the kidneys.
- Known malignancies and must not have a family history of medullary thyroid cancer.
- History of pre-RYGB hypoglycemia symptoms or low documented plasma glucose preoperatively.
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 |
|---|---|---|
| ExenatideAlso: ByettaExenatide at a dose of 5 mcg | Drug | Arm 1: Exenatide (5mcg) + Acarbose Placebo, Arm 2: Exenatide (5mcg) + Acarbose (25mg) |
| AcarboseAcarbose at a dose of 25 mg | Drug | Arm 2: Exenatide (5mcg) + Acarbose (25mg), Arm 3: Exenatide Placebo + Acarbose (25mg) |
| Exenatide PlaceboPlacebo for Exenatide | Drug | Arm 3: Exenatide Placebo + Acarbose (25mg) |
| Acarbose PlaceboPlacebo for Acarbose | Drug | Arm 1: Exenatide (5mcg) + Acarbose Placebo |
Primary outcome
Glucose area under the curve (AUC) following treatment for each 4-hour test period
Time frame: During the 4-hour test period
Each time point (15, 30, 45, 60, 90, 120, 180 and 240 minutes) will be used to calculate AUC using the trapezoidal method.
Presence of hypoglycemia
Time frame: 15, 30, 45, 60, 90, 120, 180 and 240 minutes
If at each time-point (15, 30, 45, 60, 90, 120, 180 and 240 minutes) plasma glucose is <60 mg/dL, participants will be defined as hypoglycemic
3 secondary outcomes
Minimum post-prandial blood sugar level (mg/dL)
Time frame: post meal test
Change in post-prandial blood glucose from 0min to 120min
Time frame: 0min to 120min
Change in post-prandial Insulin levels (mcg/mL)
Time frame: 0min to 120min
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2021.
Related trials for Hyperinsulinemic Hypoglycemia
Not yet recruiting
Umbilical Cord Glucose
Congenital Hyperinsulinism (CHI)
Active, not recruitingPhase 2
HM15136 (Efpegerglucagon) Treatment for 8 Weeks in Subjects Aged ≥2 Years With Congenital Hyperinsulinism (CHI)
Congenital Hyperinsulinism
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
RecruitingPhase 2
18FluoroLDOPA PET Imaging for the Detection and Localization of Focal Congenital Hyperinsulinism
Congenital Hyperinsulinism
RecruitingPhase 3
18F-DOPA II - PET Imaging Optimization
Congenital Hyperinsulinism, Neuroblastoma
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.
Shalamar D Sibley, MD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Exenatide and Acarbose in people with Hyperinsulinemic Hypoglycemia, run by University of Minnesota 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 8 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: finished, as of the sponsor's last update on 6 May 2021. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Glucose area under the curve (AUC) following treatment for each 4-hour test period (time frame: During the 4-hour test period). The study lists 2 primary outcomes in all. 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 6 May 2021.