The Effect of rs7903146 Genotype on Islet GLP-1 Production in Humans
Study on Genetic Predisposition and Islet GLP-1 Production
Plain English Summary
The Effect of rs7903146 Genotype on Islet GLP-1 Production in Humans is a Phase 2 clinical trial sponsored by Mayo Clinic studying Genetic Predisposition, Type2diabetes. Tests how a specific gene affects islet GLP-1 production in humans. For people with the TT or CC genotype at rs7903146, who do not have type 2 diabetes. Participation involves taking a GLP-1 receptor blocker or a placebo for a few days. Alternative treatments include lifestyle changes and other medications. The trial aims to enroll 80 participants.
Official Summary
The investigators recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. These effects are more pronounced in people with early type 2 diabetes (T2DM) in keeping with increased expression of PC-1/3 and GLP-1 that is observed in diabetic islets. However, its regulation is at present unknown. Common genetic variation in the TCF7L2 locus (T-allele at rs7903146) arguably confers the greatest genetic risk of T2DM. It is associated with α- and β-cell dysfunction. TCF7L2 (the product of TCF7L2) was first described as the transcription factor necessary for proglucagon expression in intestinal L-cells (which secrete GLP-1). This led to speculation that TCF7L2 confers risk of diabetes via changes in circulating GLP-1. This has turned out to not be the case. This raises the possibility that these diabetogenic effects are mediated via an inability of islet GLP-1 to adapt to rising glycemia. Therefore, this experiment will determine the contribution of islet GLP-1 to the functional abnormalities of the islet associated with the TCF7L2 locus.
Who Can Participate
Here is what you need to know about eligibility for this trial. Eligible if you have the TT or CC genotype at rs7903146. Not eligible if you are under 25 or over 70, have a CT genotype, or have high HbA1c levels. Not eligible if you are taking glucose-lowering drugs or are pregnant. Not eligible if you have had certain surgeries or have active illnesses. This trial is studying Genetic Predisposition, Type2diabetes, so participants generally need a confirmed diagnosis.
What They're Measuring
The study measures changes in glucose and glucagon levels, which can help understand how the gene affects islet function. The specific primary outcome measures are: Change in fasting glucose (Change in average glucose concentration between -30 min and 0 min of each study day (saline day vs. exendin 9-39 day)); Change in fasting glucagon (Change in average glucagon concentration between -30 min and 0 min of each study day (saline day vs. exendin 9-39 day)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.
About This Phase
This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.
Why This Trial Matters
This trial aims to understand how a specific gene affects islet GLP-1 production, filling a gap in our knowledge about type 2 diabetes. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Genetic Predisposition, Type2diabetes, where improved treatment options are needed.
Investor Insight
The market for diabetes treatments is large, and this trial could provide valuable insights that may lead to new therapies. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.
Is This Trial Right for Me?
Ask your doctor if you have the TT or CC genotype at rs7903146. You will need to fast and take a GLP-1 receptor blocker or a placebo for a few days. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.
AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.
Study Design
- Study Type: INTERVENTIONAL
- Allocation: RANDOMIZED
- Model: CROSSOVER
- Masking: NONE
- Enrollment: 80 participants
Interventions
- BIOLOGICAL: Exendin 9-39 — A competitive antagonist of the GLP-1 receptor
- OTHER: Saline — Saline infusion will serve as an inactive comparator
Primary Outcomes
- Change in fasting glucose (Change in average glucose concentration between -30 min and 0 min of each study day (saline day vs. exendin 9-39 day))
- Change in fasting glucagon (Change in average glucagon concentration between -30 min and 0 min of each study day (saline day vs. exendin 9-39 day))
Secondary Outcomes
- Change in fasting insulin (Change in average insulin concentration between -30 min and 0 min of each study day (saline day vs. exendin 9-39 day))
- Change in first phase insulin secretion (Change in integrated insulin concentrations (area above baseline) between 0 min and 30 min of each study day (saline day vs. exendin 9-39 day))
Full Eligibility Criteria
Inclusion Criteria: * Subjects with the TT or CC genotype at rs7903146 Exclusion Criteria: 1. Age \< 25 or \> 70 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose). 2. CT genotype at rs7903146 3. HbA1c \> 6.5% 4. Use of any glucose-lowering agents including metformin or sulfonylureas. 5. For female subjects: positive pregnancy test at the time of enrollment or study. 6. History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy. 7. Active systemic illness or malignancy. 8. Symptomatic macrovascular or microvascular disease.
Trial Locations
- Mayo Clinic in Rochester, Rochester, Minnesota, United States
Frequently Asked Questions
What is clinical trial NCT06972407?
NCT06972407 is a Phase 2 INTERVENTIONAL study titled "The Effect of rs7903146 Genotype on Islet GLP-1 Production in Humans." It is currently not yet recruiting and is sponsored by Mayo Clinic. The trial targets enrollment of 80 participants.
What conditions does NCT06972407 study?
This trial investigates treatments for Genetic Predisposition, Type2diabetes. The primary condition under study is Genetic Predisposition.
What treatments are being tested in NCT06972407?
The interventions being studied include: Exendin 9-39 (BIOLOGICAL), Saline (OTHER). A competitive antagonist of the GLP-1 receptor
What does Phase 2 mean for NCT06972407?
Phase 2 trials test whether the treatment works for the intended condition. They involve 100-300 patients and continue to evaluate safety while measuring effectiveness.
What is the current status of NCT06972407?
This trial is currently "Not Yet Recruiting." It started on 2026-10-01. The estimated completion date is 2029-03-01.
Who is sponsoring NCT06972407?
NCT06972407 is sponsored by Mayo Clinic. The sponsor is responsible for funding, designing, and overseeing the clinical trial.
How many people can participate in NCT06972407?
The trial aims to enroll 80 participants. The trial has not yet started recruiting.
How is NCT06972407 designed?
This is a interventional study, uses randomized allocation, follows a crossover design, employs none masking.
What are the primary outcomes being measured in NCT06972407?
The primary outcome measures are: Change in fasting glucose (Change in average glucose concentration between -30 min and 0 min of each study day (saline day vs. exendin 9-39 day)); Change in fasting glucagon (Change in average glucagon concentration between -30 min and 0 min of each study day (saline day vs. exendin 9-39 day)). These are the main endpoints researchers use to determine whether the treatment is effective.
Where is NCT06972407 being conducted?
This trial is being conducted at 1 site, including Rochester, Minnesota (United States).
Where can I find official information about NCT06972407?
The official record for NCT06972407 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT06972407. This government database provides the most up-to-date and detailed information about the trial.
What is NCT06972407 testing in simple terms?
Tests how a specific gene affects islet GLP-1 production in humans. For people with the TT or CC genotype at rs7903146, who do not have type 2 diabetes.
Why is this trial significant?
This trial aims to understand how a specific gene affects islet GLP-1 production, filling a gap in our knowledge about type 2 diabetes.
What are the potential risks of participating in NCT06972407?
Possible side effects include nausea and headache, but they are usually mild. Tell your doctor about any other medications you are taking. As with any clinical trial, participants are closely monitored and can withdraw at any time.
Should I consider participating in NCT06972407?
Ask your doctor if you have the TT or CC genotype at rs7903146. You will need to fast and take a GLP-1 receptor blocker or a placebo for a few days. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.
What does NCT06972407 signal from an investment perspective?
The market for diabetes treatments is large, and this trial could provide valuable insights that may lead to new therapies. This is a Phase 2 trial, which is focused on confirming efficacy before larger pivotal studies.
What happens if the treatment in this trial doesn't work?
Participation involves taking a GLP-1 receptor blocker or a placebo for a few days. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.
Related Conditions
More Genetic Predisposition Trials
This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.