Ondansetron for Indigestion in Diabetics

Overseen By Adil E Bharucha, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Opiates, MAO inhibitors, GLP-1 agonists, others

Disqualifiers: Cardiovascular, Renal, Hepatic, Neurological, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the medication ondansetron (also known as Zofran) affects digestion in people with diabetes who experience indigestion. Researchers aim to understand why individuals with diabetes often have stomach issues, particularly whether their symptoms link to how their bodies react to nutrients in the small intestine. Participants will be divided into groups to receive either ondansetron or a placebo for comparison. The trial seeks individuals who have had diabetes for at least three years and experience symptoms like feeling full quickly or discomfort after eating. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires stopping certain medications like opiates, alpha adrenergic agonists, metoclopramide, monoamine oxidase inhibitors, more than one serotonergic medication, and high doses of anticholinergic agents if it's medically safe. These should be discontinued for a period of four half-lives before the study assessments.

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

Research shows that ondansetron, the treatment under study, is generally safe. Studies have found it effective for managing symptoms like nausea and vomiting and well-tolerated by patients. For example, one study found ondansetron effective over several treatment cycles without causing major side effects. This suggests it is a safe choice for individuals with stomach issues, including those with diabetic gastroenteropathy.

Additionally, ondansetron has FDA approval for other uses, such as preventing nausea in children over 4 years old, which further supports its safety. While some side effects like constipation or headaches can occur, they are usually mild and manageable. Overall, existing research and its FDA approval for other uses suggest that ondansetron is well-tolerated in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for indigestion?

Researchers are excited about using Ondansetron for indigestion in diabetics because it offers a fresh approach compared to standard treatments like antacids or prokinetic agents. Unlike those options, Ondansetron works by blocking serotonin receptors, which could help manage the discomfort associated with diabetic gastroenteropathy, a condition often resistant to typical indigestion remedies. Additionally, Ondansetron is already well-known for its safety profile in treating nausea, making it a promising candidate for addressing indigestion in this unique patient group.

What evidence suggests that ondansetron might be an effective treatment for indigestion in diabetics?

Research has shown that ondansetron, which participants in this trial may receive, might help people with diabetes who experience indigestion by reducing feelings of fullness during certain tests. However, it has not consistently improved everyday symptoms compared to a placebo, another treatment option in this trial. For non-ulcer dyspepsia, ondansetron appears to help the stomach manage food more effectively. It can aid the stomach in relaxing after eating, potentially reducing discomfort. Overall, ondansetron shows promise in specific situations, but its effects can vary depending on the condition. ^{1 2 5 6 7}

Who Is on the Research Team?

Adil Bharucha, MBBS, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with diabetes (Type 1 or Type 2) and indigestion symptoms that started or worsened after their diabetes diagnosis. Participants must be able to eat test meals and not be pregnant, breastfeeding, or have a structural cause for symptoms. Those with significant health issues, certain heart conditions, allergies to eggs, or on specific medications are excluded.

Inclusion Criteria

I have had diabetes for over 3 years and my stomach discomfort started or got worse after my diagnosis.

Able to communicate adequately with the investigator and to comply with the requirements for the entire study, including the willingness and ability to consume the components of the test meals

I am a healthy male or a female not pregnant or breastfeeding.

Exclusion Criteria

I am experiencing symptoms of a stomach or bowel problem.

I am not currently using certain medications or can stop them safely before the study.

I have not had major abdominal surgery, except for minor procedures like appendectomy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Ondansetron or placebo during gastric emptying and duodenal infusion, followed by oral administration three times a day for weeks 3-6

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ondansetron
• Placebo

Trial Overview The study tests the effects of Ondansetron (8mg), an anti-nausea medication, against a placebo in managing gastrointestinal discomfort in people with both indigestion and diabetes. It aims to understand if this drug can reduce sensitivity to nutrients causing these symptoms.

How Is the Trial Designed?

Group I: Non-ulcer dyspepsia (NUD) Ondansetron 8 mg Experimental Treatment 1 Intervention

Oral Ondansetron 8 mg administered in a single does dose during gastric emptying and duodenal infusion. Oral Ondansetron 8 mg administered three times a day for weeks 3-6

Group II: Healthy Control Ondansetron 8 mg Experimental Treatment 1 Intervention

Oral Ondansetron 8 mg administered in a single does dose during gastric emptying and duodenal infusion.

Group III: Diabetic (DM) gastroenteropathy Ondansetron 8 mg Experimental Treatment 1 Intervention

Oral Ondansetron 8 mg administered in a single does dose during gastric emptying and duodenal infusion. Oral Ondansetron 8 mg administered three times a day for weeks 3-6

Group IV: Diabetic (DM) gastroenteropathy Placebo Placebo Group 1 Intervention

Oral matched placebo administered in a single does dose during gastric emptying and duodenal infusion. Oral matched placebo administered three times a day for weeks 3-6

Group V: Healthy Control Placebo Placebo Group 1 Intervention

Oral matched placebo administered in a single does dose during gastric emptying and duodenal infusion.

Group VI: Non-ulcer dyspepsia (NUD) Placebo Placebo Group 1 Intervention

Oral matched placebo administered in a single does dose during gastric emptying and duodenal infusion. Oral matched placebo administered three times a day for weeks 3-6

Ondansetron is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Zofran for:

• Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy
• Prevention of postoperative nausea and/or vomiting

Approved in European Union as Zofran for:

• Prevention of nausea and vomiting associated with chemotherapy
• Prevention of postoperative nausea and vomiting

Approved in Canada as Zofran for:

• Prevention of nausea and vomiting associated with chemotherapy
• Prevention of postoperative nausea and vomiting

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

A recent study found no evidence that the anti-nausea drug Zofran (ondansetron) increases the risk of birth defects in children.

This finding suggests that Zofran can be considered safe for use during pregnancy regarding concerns about congenital anomalies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morning sickness drug is not linked to increased risk of birth defects. [2017]

In a phase II study involving 25 patients undergoing cisplatin chemotherapy, ondansetron effectively controlled nausea and vomiting, achieving 'good' control rates of 64-100% for vomiting and 88-100% for nausea.

Ondansetron was well tolerated with minimal side effects, indicating it is a safe option for preventing chemotherapy-induced nausea and vomiting, although further randomized studies are recommended for comparison with standard anti-emetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of oral and intravenous ondansetron in patients treated with cisplatin. Khoo, KS., Ang, PT., Soh, LT., et al.[2020]

Ondansetron effectively controlled acute emesis in 53% of patients on a specific dosing schedule after non-cisplatin-based chemotherapy, demonstrating its potential as a treatment for those previously resistant to standard antiemetics.

The drug maintained its antiemetic efficacy across multiple treatment cycles, with no major toxicity reported, making it a safe option for patients experiencing chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The 5-HT3 receptor antagonist ondansetron re-establishes control in refractory emesis induced by non-cisplatin chemotherapy. Seynaeve, C., de Mulder, PH., Lane-Allman, E., et al.[2019]

In a study involving 36 patients undergoing chemotherapy with cisplatin, fast dissolving ondansetron (Zofran Zydis) demonstrated a 75% complete response rate in preventing nausea and vomiting.

This new formulation is particularly beneficial for patients who have difficulty swallowing traditional oral antiemetics, making it an effective addition to antiemetic treatments for chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Freeze dried ondansetron: first observations with the fast dissolving oral antiemetic Zofran Zydis for the prophylaxis of the cisplatin-induced emesis in gynecological cancer patients. Lehoczky, O., Udvary, J., Pulay, T.[2013]

In a study of 35 children undergoing highly emetogenic chemotherapy, ondansetron was found to be highly effective in preventing nausea and vomiting, achieving complete or major responses in 85.3% of patients without cisplatin and 71.4% with cisplatin, compared to only 38.8% with traditional antiemetics.

Ondansetron was administered at lower than recommended doses for 85 days without any adverse effects, indicating it is a safe and effective antiemetic option, especially since it does not cause sedation and was well-received by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ondansetron as an effective drug in prophylaxis of chemotherapy--induced emesis in children. Kołecki, P., Wachowiak, J., Beshari, SE.[2013]

Ondansetron has been shown to be safe and well-tolerated in approximately 1,400 cancer patients and 650 other volunteers, with the main side effects being mild constipation and headache.

The drug has a wide therapeutic index, does not interact with commonly prescribed medications, and has no reported dependence or extrapyramidal side effects, making it a reliable option for anti-emetic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of ondansetron. Smith, RN.[2013]

In a study of 28 cancer patients, ondansetron significantly reduced nausea and vomiting caused by cisplatin treatment, with the median time to the first vomiting episode extending from 2.8 hours in the placebo group to 11.6 hours in the ondansetron group.

Ondansetron was found to be safe, with no adverse effects reported, and it effectively eliminated the need for additional antiemetic treatments in patients, demonstrating its efficacy as a serotonin S3 receptor antagonist.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of ondansetron (GR 38032F) and the role of serotonin in cisplatin-induced nausea and vomiting. Cubeddu, LX., Hoffmann, IS., Fuenmayor, NT., et al.[2013]

In a study of 40 patients with advanced tumors receiving various chemotherapy regimens, ondansetron demonstrated a strong prophylactic antiemetic effect, particularly in the CHOP group, where 64% experienced full control of nausea and vomiting.

No significant side effects were reported from ondansetron treatment, indicating it is a safe option for managing chemotherapy-induced nausea and loss of appetite in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Novel pharmacologic form of ondansetron (Zofran)--lingual tablets in the prevention of cytostatic chemotherapy-induced loss of appetite, nausea and vomiting]. Gershanovich, ML., Beresneva, IA., Makhnova, EV.[2015]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38946172/

Effects of ondansetron on symptoms during a gastric emptying ... Ondansetron significantly reduced fullness during enteral lipid infusion in patients with DGE. Overall, ondansetron did not improve daily ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11321918/

Effects of Ondansetron on Symptoms during a Gastric ... This study compared the effects of ondansetron and placebo in patients with diabetes mellitus and symptoms of dyspepsia (diabetic gastroenteropathy [DGE]).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03865290?cond=Diabetes&spons=NIDDK&aggFilters=status:not%20rec%20act&viewType=Table&rank=6

Effects of Ondansetron on Gastrointestinal Sensorimotor ... The primary objectives of this study are to evaluate the effects of ondansetron, on symptoms (i) during a gastric emptying study, (ii) during enteral lipid ...

4. withpower.com withpower.com/trial/phase-3-diabetes-mellitus-3-2019-3e591

Ondansetron for Indigestion in Diabetics Trial Overview The study tests the effects of Ondansetron (8mg), an anti-nausea medication, against a placebo in managing gastrointestinal discomfort in people ...

5. researchgate.net researchgate.net/publication/381852664_Effects_of_ondansetron_on_symptoms_during_a_gastric_emptying_study_and_enteral_lipid_challenge_and_on_daily_symptoms_in_diabetic_gastroenteropathy

Effects of ondansetron on symptoms during a gastric ... Overall, ondansetron did not improve daily symptoms versus placebo. But patients in whom ondansetron improved symptoms during enteral lipid ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8192258/

Diabetic gastroenteropathy: An underdiagnosed complication This article is an extensive review that provides an update on the pathophysiology, symptoms, diagnosis, and treatment of diabetic gastroenteropathy.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2255534X24001002

Review article Gastrointestinal adverse effects of old and ... Some of which can cause significant gastrointestinal adverse effects, such as dyspepsia, nausea, vomiting, bloating, diarrhea, and constipation.