Gastric Bypass and Sleeve Gastrectomy for Hypoglycemia

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

Must not be taking: Atropine interactors

Disqualifiers: Heart, lung, liver, kidney, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how two types of weight-loss surgeries, gastric bypass and sleeve gastrectomy, affect blood sugar levels and insulin after eating. Researchers are investigating the roles of hormones and nerves in these changes. The trial includes two groups: one receives Exendin-(9-39), a hormone-based treatment, to assess its effects on insulin and glucose, while the other receives atropine, a medication affecting nerve signals, to study its impact on nerves and blood sugar. Individuals who have undergone gastric bypass surgery and experience very low blood sugar, or those who have had bariatric surgery without symptoms, might be suitable for this study. Participants must be able to travel to Cedars-Sinai Medical Center. As an Early Phase 1 trial, this study aims to understand how these treatments work in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but 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 both treatments tested in this trial have undergone safety studies. Exendin-(9-39) has been evaluated for patient tolerance, with results indicating it is generally safe and can help manage low blood sugar after surgery. Some studies have also examined how the body absorbs and processes this drug, with promising findings.

Atropine has long been used in other medical situations, such as eye exams. It is known to cause side effects like blurry vision and sensitivity to light. In rare cases, it can lead to more serious effects, such as low blood pressure or a fast heartbeat.

Both treatments have undergone initial tests, but this trial remains in its early stages. Much remains to be learned about their safety for this new use. However, existing research provides a solid foundation for understanding their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments being explored for hypoglycemia after gastric bypass and sleeve gastrectomy because they target the underlying biological processes differently than current options. Exendin-(9-39) is unique as it focuses on the GLP-1 hormone, which plays a crucial role in regulating glucose metabolism and insulin secretion, especially after eating. On the other hand, Atropine is being studied for its potential to influence insulin secretion and glucose metabolism by affecting neural activation. These approaches are distinct from standard treatments that typically involve dietary changes or medication, offering a more targeted intervention for managing hypoglycemia.

What evidence suggests that this trial's treatments could be effective for hypoglycemia?

In this trial, Exendin-(9-39) is one of the treatments under study. Research has shown that Exendin-(9-39) can help manage low blood sugar levels, with one study indicating it reduced the risk of hypoglycemia by 82%. This suggests it might effectively prevent blood sugar drops after eating.

Atropine is another treatment option in this trial. Studies indicate that Atropine can slow the stomach's emptying during low blood sugar events, which could help maintain stable glucose levels. Atropine has also improved the body's response to insulin. Both treatments show promise for managing blood sugar in different ways. ^{6 7 8 9 10}

Who Is on the Research Team?

Marzieh Salehi, MD, MS

Principal Investigator

The University of Texas Health Science Center at San Antonio

Are You a Good Fit for This Trial?

This trial is for individuals who've had bariatric surgery and are asymptomatic, can visit Cedars-Sinai Medical Center, and don't have a personal history of diabetes. It's not for those with enlarged prostates, pregnant women, anyone unable to consent, diabetics, or people with certain medical conditions like uncontrolled hypertension or serious organ diseases.

Inclusion Criteria

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

I have had weight loss surgery and feel no symptoms.

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

Exclusion Criteria

I am not on medications that interact with atropine or can stop them if needed.

I have a history of glaucoma.

I am unable to understand and agree to the study's procedures and risks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo gastric bypass surgery or sleeve gastrectomy to study effects on glucose metabolism

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after surgery, focusing on glucose metabolism and insulin secretion

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atropine
• Exendin-(9-39)
• Gastric Bypass Surgery
• Sleeve Gastrectomy

Trial Overview The study investigates how gastric bypass and sleeve gastrectomy affect blood sugar control after eating by looking at neural and hormonal responses. Participants will be given Exendin-(9-39) or Atropine to see the effects on glucose metabolism.

How Is the Trial Designed?

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

To evaluate the role of GLP-1 on glucose metabolism and insulin secretin after glucose and protein ingestion.

Group II: Atropine Experimental Treatment 1 Intervention

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

Gastric Bypass Surgery is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Roux-en-Y Gastric Bypass for:

• Severe obesity with BMI ≥35 kg/m²
• Type 2 diabetes with BMI ≥30 kg/m²
• Obesity-related comorbidities such as hypertension, hyperlipidemia, obstructive sleep apnea, and GERD

Approved in European Union as Roux-en-Y Gastric Bypass for:

• Severe obesity with BMI ≥35 kg/m²
• Type 2 diabetes with BMI ≥30 kg/m²
• Obesity-related comorbidities such as hypertension, hyperlipidemia, obstructive sleep apnea, and GERD

Approved in Canada as Roux-en-Y Gastric Bypass for:

• Severe obesity with BMI ≥35 kg/m²
• Type 2 diabetes with BMI ≥30 kg/m²
• Obesity-related comorbidities such as hypertension, hyperlipidemia, obstructive sleep apnea, and GERD

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study of 47 females without diabetes undergoing Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), both surgeries resulted in lower fasting glucose levels but increased glycemic variability (GV) after 6 and 12 months.

56% of RYGB and 75% of SG patients experienced interstitial glucose concentrations below 3.9 mmol/L after 12 months, with about 70% of these patients reporting hypoglycemic symptoms, indicating a potential risk for hypoglycemia post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycemic variability and hypoglycemia before and after Roux-en-Y Gastric Bypass and Sleeve Gastrectomy - A cohort study of females without diabetes. Nilsen, I., Sundbom, M., Osterberg, J., et al.[2023]

In a study of 120 patients who underwent either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG), reactive hypoglycemia occurred in 29% of RYGB patients compared to 14% of SG patients, indicating a higher risk associated with RYGB.

RYGB was linked to more severe hypoglycemic episodes and a decrease in dynamic β-cell glucose sensitivity, suggesting that it may lead to inappropriate insulin secretion in response to glucose changes, while both procedures improved overall insulin sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of Hypoglycemia After Gastric Bypass vs Sleeve Gastrectomy: A Randomized Trial. Capristo, E., Panunzi, S., De Gaetano, A., et al.[2018]

Patients who experienced hypoglycemic syndrome after Roux-en-Y gastric bypass surgery (RYGB) showed insulin secretion rates similar to those of insulin-sensitive individuals, indicating that their insulin response is appropriate despite their condition.

The study found that RYGB patients had lower pancreatic beta-cell sensitivity to glucose compared to other groups, suggesting that the hypoglycemic syndrome is not due to excessive insulin secretion but rather a specific response to glucose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucose-stimulated insulin secretion in gastric bypass patients with hypoglycemic syndrome: no evidence for inappropriate pancreatic beta-cell function. Kim, SH., Abbasi, F., Lamendola, C., et al.[2022]

A carbohydrate-restricted diet (CRD) significantly reduced the frequency of hypoglycemic events in 41 patients who had undergone Roux-en-Y gastric bypass surgery, decreasing events from an average of 17.1 to 2.5 per month, which is an 85% reduction.

The CRD also improved the lowest blood glucose levels during hypoglycemic events, indicating better overall glucose control, although about 34% of patients still required additional insulin therapy for adequate management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of carbohydrate restriction as primary treatment for post-gastric bypass hypoglycemia. van Meijeren, J., Timmer, I., Brandts, H., et al.[2019]

Roux-en-Y gastric bypass surgery (RYGB) significantly improves glucose control in most patients with type 2 diabetes, but can lead to a serious complication known as hyperinsulinemic hypoglycemia in a minority of individuals.

This condition arises due to rapid nutrient emptying and increased insulin and GLP-1 secretion after meals, resulting in higher glucose levels and exaggerated insulin responses, making diagnosis and treatment challenging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postprandial hypoglycemia after gastric bypass surgery: from pathogenesis to diagnosis and treatment. Honka, H., Salehi, M.[2020]

Reversing Roux-en-Y gastric bypass (RYGB) in two patients with post-RYGB hypoglycemia did not improve their condition, as both continued to experience hyperinsulinemic hypoglycemia after a mixed-meal challenge.

After the reversal, GLP-1 levels significantly decreased, while GIP levels increased dramatically, indicating that GIP may play a role in the persistence of hypoglycemia despite the surgical reversal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormonal response to a mixed-meal challenge after reversal of gastric bypass for hypoglycemia. Lee, CJ., Brown, T., Magnuson, TH., et al.[2021]

The study aims to compare the incidence of reactive hypoglycaemia between Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) over a 1-year period, as reactive hypoglycaemia is a common complication in about 72% of RYGB patients.

A secondary goal is to evaluate how each surgical procedure affects insulin sensitivity, which is important for understanding their impact on obesity-related cardiometabolic issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol for a randomised clinical study comparing the effect of Roux-en-Y gastric bypass and sleeve gastrectomy on reactive hypoglycaemia in morbidly obese subjects. Mingrone, G., Panunzi, S., De Gaetano, A., et al.[2021]

In two pilot studies involving 69 obese patients with type 2 diabetes, intensive glucose management before and after Roux-en-Y gastric bypass (RYGB) surgery did not lead to significantly better glycemic control one year post-surgery compared to conservative management.

The results suggest that while RYGB surgery itself has a strong positive impact on glucose control, additional intensive glucose-lowering interventions before or shortly after the surgery do not provide extra clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of perioperative management of glycemia in severely obese diabetic patients undergoing gastric bypass surgery. Chuah, LL., Miras, AD., Papamargaritis, D., et al.[2022]

In a study of 46 patients after Roux-en-Y gastric bypass (RYGB), those experiencing hypoglycemia (HYPO group) showed higher early insulin secretion rates but lower late insulin secretion rates compared to those without hypoglycemia (NONHYPO group) during an oral glucose tolerance test.

Continuous glucose monitoring revealed that HYPO patients spent more time with glucose levels below 3.3 mmol/L in real life, indicating a need for careful monitoring of this patient group post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-prandial hypoglycemia results from a non-glucose-dependent inappropriate insulin secretion in Roux-en-Y gastric bypassed patients. Vaurs, C., Brun, JF., Bertrand, M., et al.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8722071/

Atropine inhibits the increase in gastric emptying during ... Conclusions: Cholinergic muscarinic blockade with atropine inhibits the increase in gastric emptying during hypoglycemia. Vagal activity seems to be an ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/2190548/

Atropine: effects on glucose metabolism Our data indicate that glucose production significantly (p less than 0.05) increased (24.0 +/- 2.0 vs. 30.9 +/- 2.6 mumoles.kg-1.min-1) following atropine ...

3. researchgate.net researchgate.net/publication/14480486_Atropine_Inhibits_the_Increase_in_Gastric_Emptying_During_Hypoglycemia_in_Humans

Atropine Inhibits the Increase in Gastric Emptying During ... During hypoglycemia with atropine infusion, T50 was 40.7 min (range 10.0-120.0) for the liquid phase and 111.4 min (range 38.9-120.0) for the ...

4. academic.oup.com academic.oup.com/jcem/article/96/11/E1843/2833927

Atropine Improves Insulin Sensitivity in Both Lean and ... In this study we show that whole-body insulin sensitivity was higher during a short-term atropine compared with saline/placebo or physostigmine infusion in lean ...

5. researchgate.net researchgate.net/figure/Role-of-atropine-in-the-hypoglycemic-effect-of-IES-a-The-blood-glucose-during-IDGTT-b_fig4_348609501

Role of atropine in the hypoglycemic effect of IES. a ... Preclinical data are promising: intestinal electrical stimulation has been shown to reduce food intake in rats and pigs and to reduce intestinal absorption and ...

6. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=20491566-e6eb-8d4a-3083-77ea429f7bc4

Label: ISOPTO ATROPINE- atropine sulfate solution - DailyMed No overall differences in safety or effectiveness have been observed between elderly and adult patients. In the event of accidental ingestion or toxic ...

7. imgcdn.mckesson.com imgcdn.mckesson.com/CumulusWeb/Click_and_learn/SDS_9AKORN_ATROPINE_SULF_DRP_OPHTH_1PERCENT_15ML.pdf

SDS: Atropine Sulfate Ophthalmic Solution, USP 1% Severe reactions are manifested by low blood pressure (hypotension) with progressive respiratory depression. Coma and death have been reported in the very ...

8. somersetpharma.com somersetpharma.com/wp-content/uploads/2024/07/Atropine-SDS.pdf

SAFETY DATA SHEET Atropine Sulfate Ophthalmic ... Overdosage (systemic toxicity) is ma nifested by flushing and dryness of the skin (a ra sh may be present in children), blurred vision, a rapid and irregula r.

9. goodrx.com goodrx.com/atropine/what-is?srsltid=AfmBOop-hUlvlD3ZhhxvxhyFqGd_sIs2aiSXRcrwmzzAz2injur_ow4R

Atropine (Isopto Atropine): Uses, Side Effects, Dosage & ... Light sensitivity and blurry vision · Rise in blood pressure · Greater risk of side effects in people with certain medical conditions affecting the nervous system.

10. mayoclinic.org mayoclinic.org/drugs-supplements/atropine-sulfate-ophthalmic-route/description/drg-20313091

Atropine sulfate (ophthalmic route) - Side effects & dosage Atropine sulfate eye drops is used to dilate the pupil before eye exams. It is also used to treat an eye condition called amblyopia (lazy eyes) and other eye ...