Gastric Bypass Surgery for Type 2 Diabetes

Recruiting at 1 trial location

Overseen By Marzieh Salehi, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: The University of Texas Health Science Center at San Antonio

Disqualifiers: Heart, lung, liver, kidney disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how gastric bypass surgery affects insulin secretion and glucose metabolism in individuals with and without hypoglycemia (low blood sugar) post-surgery. Researchers aim to understand how the surgery might aid type 2 diabetes and why some individuals experience low blood sugar years later. The trial tests various treatments, including Atropine (used for certain nerve agent and pesticide poisonings), Exendin-(9-39) (an experimental treatment), and GLP-1 and GIP (hormones involved in insulin regulation), to assess their impact on insulin and blood sugar levels. Suitable candidates include those who have undergone gastric bypass and experience low blood sugar, those who have had the surgery without symptoms, or healthy individuals without diabetes. Participants must be able to visit the Cedars-Sinai Medical Center for the study. As an Early Phase 1 trial, this research focuses on understanding how these treatments work in people, offering participants a chance to contribute to groundbreaking medical knowledge.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking any medication that might interact with atropine and cannot be stopped, you will be excluded from the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Exendin-(9-39) has been tested in people to help manage blood sugar levels. Studies found it to be generally safe and well-tolerated, with the main goal of preventing low blood sugar. This treatment blocks signals that usually increase insulin, the hormone that lowers blood sugar.

Safety data indicates that atropine is commonly used to treat certain types of poisoning and is known for being safe. It has been used for many years, and its effects are well documented.

GLP-1 and GIP treatments are also under study for their safety. Research shows these gut hormones, which help control blood sugar, are generally well-tolerated in short-term use. They are often used in treating type 2 diabetes.

Since this trial is in an early phase, detailed safety data might be limited, but earlier studies show promising safety results for these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for type 2 diabetes, which often involve medications like metformin or insulin injections, these investigational treatments are exploring new pathways to manage the condition. Exendin-(9-39) stands out because it targets GLP-1 signaling, which plays a crucial role in glucose tolerance and insulin secretion. Atropine, on the other hand, is being tested for its potential to affect neural activation, thus influencing insulin secretion and glucose metabolism differently than existing drugs. Meanwhile, the combination of GLP-1 and GIP is intriguing to researchers because it evaluates how gut hormones can enhance beta-cell sensitivity, offering a fresh angle on maintaining blood sugar levels. These novel approaches could pave the way for more effective management of type 2 diabetes, potentially reducing reliance on traditional medication.

What evidence suggests that this trial's treatments could be effective for type 2 diabetes?

Research has shown that RYGB surgery can improve type 2 diabetes by affecting hormones and nerve signals. After surgery, the body may release more of the hormone GLP-1, which helps control blood sugar. In this trial, participants may receive Exendin-(9-39), which works with this process and has been shown in studies to help stabilize blood sugar levels. Another treatment option in this trial is Atropine, which influences nerve signals and has been found to improve insulin use. Additionally, the trial will evaluate the effects of GLP-1 and GIP, which enhance sugar management by increasing insulin release. These treatments aim to improve sugar handling after gastric bypass surgery. ^{6 7 8 9 10}

Who Is on the Research Team?

Marzieh Salehi, MD, MS

Principal Investigator

Marzieh Salehi

Are You a Good Fit for This Trial?

This trial is for individuals who've had gastric bypass surgery and either have low blood sugar episodes or are symptom-free. It's also open to healthy people without diabetes. Participants must be able to visit Cedars-Sinai Medical Center but can't join if they have certain conditions like an enlarged prostate, glaucoma, serious organ diseases, uncontrolled hypertension or cholesterol, significant anemia, or are pregnant.

Inclusion Criteria

I am healthy, have never had surgery, and do not have diabetes.

I can travel to Cedars-Sinai Medical Center for the study.

I have had low blood sugar levels below 50 mg/dl after gastric bypass surgery.

Exclusion Criteria

You have low hemoglobin levels (less than 11g/dL).

I have myasthenia gravis.

I have had gastric bypass surgery and am experiencing severe blockage or diarrhea.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive experimental treatments to evaluate the role of GLP-1 signaling, neural activation, and beta-cell sensitivity to gut hormones

6-8 weeks

Multiple visits for administration of treatments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atropine
• Exendin-(9-39)
• GLP-1 and GIP

Trial Overview

The study investigates how factors like hormones and nerves affect insulin release after gastric bypass surgery. It involves giving participants drugs such as Exendin-(9-39), Atropine, GLP-1, and GIP to see their effect on insulin secretion in those with and without post-surgery hypoglycemia compared to non-operated controls.

How Is the Trial Designed?

Group I: atropine Experimental Treatment 1 Intervention

To evaluate the effect of neural activation on insulin secretion and glucose metabolism

Group II: GLP-1 and GIP Experimental Treatment 1 Intervention

to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones

Group III: Exendin-(9-39) Experimental Treatment 1 Intervention

To evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

Published Research Related to This Trial

GLP-1-based therapies are effective for treating type 2 diabetes (T2D) and have shown a good safety profile, especially with long-acting analogs that can also be used in combination with insulin.

Recent research highlights that GLP-1 secretion increases after bariatric surgery, contributing to weight loss and diabetes remission, while GIP has important effects on bone metabolism but is not suitable for T2D therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-1 and gastric inhibitory polypeptide: new advances. Gallwitz, B.[2022]

GIP1-39, a newly identified form of gastric inhibitory polypeptide, is more effective than the previously known GIP1-42 in stimulating insulin secretion from rat pancreatic islets, indicating its potential as a stronger insulinotropic agent.

At a concentration of 100 nM, GIP1-39 significantly increases intracellular calcium levels in pancreatic beta cells and enhances insulin exocytosis, suggesting a promising mechanism for its action in promoting insulin release.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GIP1-39, a novel insulinotropic peptide form and aspects on its mechanism of action. Xie, L., Lu, J., Ostenson, CG., et al.[2018]

In a study involving 20 critically ill patients, the addition of glucose-dependent insulinotropic polypeptide (GIP) to glucagon-like peptide-1 (GLP-1) did not enhance glucose-lowering effects or insulin responses during nutrient infusion.

While GIP did cause a slight increase in glucagon levels before nutrient delivery, it ultimately did not contribute to improved glucose control in patients experiencing acute hyperglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of exogenous glucose-dependent insulinotropic polypeptide in combination with glucagon-like peptide-1 on glycemia in the critically ill. Lee, MY., Fraser, JD., Chapman, MJ., et al.[2021]

In a study involving eight fasting students, the infusion of porcine gastric inhibitory polypeptide (GIP) and glucose led to significant increases in serum insulin levels, demonstrating that insulin release is not affected by atropine.

The infusion of GIP also resulted in a significant rise in plasma pancreatic polypeptide (PP) levels when atropine was not administered, indicating that GIP may play a role in stimulating PP release during the intestinal phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of atropine on GIP-induced insulin and pancreatic polypeptide release in man. Amland, PF., Jorde, R., Burhol, PG., et al.[2019]

Initial concerns about glucose-dependent insulinotropic polypeptide (GIP) as a treatment for obesity and type 2 diabetes were based on its reduced effectiveness in insulin secretion and potential to increase glucagon and fat storage in non-diabetic individuals.

Recent studies suggest that GIP can be beneficial when glycemia is normalized, leading to the development of new GIP receptor agonists and polyagonist peptides that target GIP, GLP-1, and glucagon receptors, showing promise for improving blood sugar control and aiding weight loss in obese type 2 diabetes patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GIP analogues and the treatment of obesity-diabetes. Bailey, CJ.[2021]

Tirzepatide, approved in 2022, is a novel treatment for type 2 diabetes that acts on both GLP-1 and GIP pathways, showing significant efficacy in lowering blood sugar levels and promoting weight loss in various patient groups.

Clinical trials, including the SURPASS and SURMOUNT studies, indicate that tirzepatide has a safety profile similar to traditional GLP-1 receptor agonists, with common gastrointestinal side effects, making it a promising option for patients needing better glycemic and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. Krauss, Z., Hintz, A., Fisk, R.[2023]

In a study involving 17 healthy volunteers, GIP significantly reduced gastric emptying time and improved postprandial glucose and insulin levels, but did not affect appetite or satiety.

GLP-1, on the other hand, markedly increased gastric emptying time, reduced hunger and desire to eat, and also improved glucose regulation, suggesting it may be more beneficial for weight loss in type 2 diabetes treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis. Edholm, T., Degerblad, M., Grybäck, P., et al.[2022]

The hybrid peptide 19W, which activates both GLP-1 and GIP receptors, showed improved stability and effectiveness in stimulating insulin secretion and glucose tolerance in mice, indicating its potential as a treatment for diabesity.

In a 28-day study with high fat-fed mice, 19W significantly reduced food intake, body weight, and fasting blood glucose levels, while also improving liver health, suggesting it could be a promising oral therapy for obesity and diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An oral GLP-1 and GIP dual receptor agonist improves metabolic disorders in high fat-fed mice. Ma, T., Lu, W., Wang, Y., et al.[2022]

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