Domperidone for Gastrointestinal Disorders

Overseen By Mehnaz Shafi

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antiarrhythmics, MAO inhibitors

Disqualifiers: Cardiac diagnoses, Liver failure, Electrolyte disorders, GI hemorrhage, Prolactinoma, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of domperidone in treating individuals with gastrointestinal disorders. Domperidone may relieve symptoms like pain, bloating, and nausea by promoting stomach contractions to empty food more effectively. The trial seeks participants with gastrointestinal issues that have not improved with standard treatments, such as gastroparesis (delayed stomach emptying), difficult-to-treat acid reflux, or severe indigestion. Participants must have undergone evaluations to rule out other causes of their symptoms and agree to use domperidone as the study drug. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the validation of a promising treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain heart medications or MAO inhibitors. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that domperidone is likely to be safe for humans?

Research has shown that domperidone is generally safe for treating stomach problems. In studies involving 1,221 patients with conditions like slow stomach emptying, indigestion, and acid reflux, domperidone was well-tolerated. Most participants did not experience serious side effects.

Domperidone is already used in Canada for stomach issues, supporting its safety. Some side effects may include dry mouth, headache, or dizziness, but these are uncommon. Clinical data indicate that domperidone is usually safe for most people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Domperidone is unique because it offers an alternative approach to managing gastrointestinal disorders by enhancing gut motility. Unlike standard treatments like proton pump inhibitors or antacids, which primarily focus on reducing stomach acid, domperidone works by blocking dopamine receptors, which helps accelerate the movement of food through the stomach and intestines. Researchers are excited about domperidone because it has the potential to alleviate symptoms more effectively for patients who do not respond well to current options. Additionally, its targeted mechanism may result in fewer systemic side effects compared to some existing treatments.

What evidence suggests that domperidone might be an effective treatment for gastrointestinal disorders?

Research has shown that domperidone, the treatment under study in this trial, can alleviate stomach and digestion problems. Studies have found that domperidone helps the stomach move food into the intestines more quickly, with about 60% of studies finding it effective for this purpose. Additionally, 67% of studies indicated it reduced hospital visits for people with related issues. Domperidone has proven more effective than a placebo in treating gastroparesis, a condition where the stomach empties too slowly. These findings suggest that domperidone can help manage symptoms like pain, bloating, and nausea. ^{3 6 7 8 9}

Who Is on the Research Team?

Mehnaz Shafi

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with chronic gastrointestinal disorders like gastroparesis, severe heartburn, or indigestion that haven't improved with standard treatments. They must have stable blood counts and organ function, no other causes for their symptoms after a full check-up, and agree to the study's terms. It's not open to pregnant women, those on certain heart drugs or MAO inhibitors, people allergic to domperidone, or anyone with specific heart conditions or severe liver issues.

Inclusion Criteria

I have agreed to take the study drug, domperidone, by signing a consent form.

Your hemoglobin level is at least 8.0 grams per deciliter and not changing.

I have severe stomach issues like gastroparesis, GERD, or dyspepsia.

Exclusion Criteria

I am taking medication that affects my heart's rhythm.

I have a history of or currently have liver failure.

I am not pregnant or breastfeeding, and if capable of becoming pregnant, I agree to use birth control during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive domperidone orally thrice daily or four times daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Domperidone

Trial Overview The trial is testing how effective domperidone is in treating chronic gastrointestinal disorders by seeing if it can help control symptoms such as pain, bloating, nausea and vomiting. This involves taking the medication and completing questionnaires about symptom changes.

How Is the Trial Designed?

Group I: Treatment (domperidone) Experimental Treatment 2 Interventions

Patients receive domperidone PO TID or QID. Treatment continues in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Motilium for:

• Nausea and vomiting
• Gastroparesis
• Gastrointestinal motility disorders

Approved in Canada as Motilium for:

• Nausea and vomiting
• Gastroparesis
• Gastrointestinal motility disorders

Approved in United States as Domperidone for:

• Severe and treatment-refractory gastrointestinal motility problems (under expanded access IND)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Domperidone is effective in relieving symptoms of gastrointestinal motility disorders, particularly diabetic gastroparesis, showing better symptom relief than placebo and similar efficacy to other prokinetic drugs like metoclopramide and cisapride.

With minimal central nervous system penetration, domperidone has a favorable safety profile, making it a safer alternative to metoclopramide, with rare reports of adverse effects such as dystonic reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Domperidone: a peripherally acting dopamine2-receptor antagonist. Barone, JA.[2017]

Domperidone (Motilium) is as effective as other well-known anti-emetics like Daedalon (Dramamin) and Torecan in preventing nausea and vomiting after surgery, based on a comparative study.

Domperidone is particularly advantageous due to its oral administration route and lack of toxic effects, making it a favorable option for postoperative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The importance of domperidone (Motilium) in controlling postoperative nausea and vomiting. Lencz, L.[2013]

In a study of 73 gynecological patients, domperidone effectively controlled various dyspeptic symptoms, nausea, vomiting, climacteric flushes, and migraine prevention in 67.1% of cases.

The drug showed a significant gastrokinetic and antiemetic effect, suggesting it can be used alone or alongside other treatments for migraines and climacteric symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Some possible gynaecological indications for peripheral antidopamine therapy. Varga, A., Lovas, J.[2013]

In a study involving 57 patients recovering from acute myocardial infarction, domperidone (Motilium) effectively prevented nausea, vomiting, and gastroduodenal complaints during the recovery period.

Domperidone was found to promote bowel movement and defecation without causing cardiac or other toxic effects, making it a safe option for patients in intensive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of domperidone in improving intestinal activity in acute myocardial infarction patients. Lencz, L.[2013]

A randomized, double-blind, placebo-controlled trial involving 208 patients with functional dyspepsia showed that combining compound azintamid with domperidone significantly improved symptoms compared to domperidone alone, with a response rate of 89.2% in the combination group versus 76.4% in the control group.

The combination therapy led to greater reductions in bloating and pain intensity, as well as improved patient satisfaction, without any severe side effects, suggesting it is a safe and effective treatment option for functional dyspepsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combination therapy of azintamid and domperidone in functional dyspepsia: a randomised, double-blind, placebo-controlled trial]. Zhao, L., Xu, L., Li, Q., et al.[2014]

Domperidone (Motilium) is effective in treating dyspepsia and emesis in women, with a study involving 68 women with dyspepsia and 94 cases of emesis showing good tolerance and no interference with gynaecological treatments.

The drug's antiemetic effect is influenced by the timing of intake, which can be a limitation for oral administration, but it remains a preferred option for managing upper gastroduodenal motility disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of peripheral dopamine antagonist (Motilium) in the treatment of dyspeptic complaints of different origin and in nausea, vomiting. Sásdi, A.[2013]

In a study of 100 children aged 5-12 with abdominal pain predominant functional gastrointestinal disorders, those treated with domperidone showed a significant improvement in symptoms compared to the placebo group, with 74% reporting general improvement after 8 weeks.

Domperidone also led to a notable reduction in abdominal pain severity and an increase in gastric motility, with no reported adverse effects, suggesting it is a safe and effective treatment option for these children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Controlled Clinical Trial on Value of Domperidone in Functional Abdominal Pain in Children. Karunanayake, A., Devanarayana, NM., de Silva, A., et al.[2019]

A significant number of patients (69.7%) receiving domperidone were also prescribed QT-interacting medications, which can increase the risk of life-threatening arrhythmias due to QT prolongation.

Inconsistent EKG monitoring was observed, with 15.3% of patients showing QT prolongation at the start of treatment and 32.5% at follow-up, highlighting the need for better monitoring to prevent cardiac risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Domperidone is Commonly Prescribed With QT-Interacting Drugs: Review of a Community-based Practice and a Postmarketing Adverse Drug Event Reporting Database. Ehrenpreis, ED., Roginsky, G., Alexoff, A., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10981152/

Safety of prolonged use of metoclopramide and domperidone ... These pharmacologic actions may lead to improved GI peristalsis and increased gastric emptying. Despite their effectiveness both metoclopramide ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0016508522013981

Efficacy and Safety of Drugs for Gastroparesis We studied efficacy of drugs for gastroparesis. Most drugs were not efficacious; only clebopride and domperidone were better than a placebo. There is a great ...

3. cghjournal.org cghjournal.org/article/S1542-3565(08)00241-3/fulltext

A Systematic Review of the Efficacy of Domperidone ... Sixty percent of the studies showed an efficacy in gastric emptying and 67% of the studies proved the drug effective in reducing hospital admissions.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01696734

Domperidone in Treating Patients With Gastrointestinal ... This phase III trial studies how well domperidone works in treating patients with gastrointestinal disorders.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9505562/

Efficacy and Safety of Domperidone in Combination with ... In conclusion, the combination of domperidone and a PPI is generally safe and effective in treating GERD as compared with that of PPI alone.

6. mayoclinic.org mayoclinic.org/drugs-supplements/domperidone-oral-route/description/drg-20063481

Domperidone (oral route) - Side effects & dosage Domperidone is a medicine that increases the movements or contractions of the stomach and bowel. Domperidone is also used to treat nausea and vomiting.

7. medsafe.govt.nz medsafe.govt.nz/profs/datasheet/m/motiliumtab.pdf

MOTILIUM® Clinical Trial Data​​ The safety of MOTILIUM was evaluated in 1221 patients with gastroparesis, dyspepsia, gastro-oesophagoeal reflux disorder (GERD), or other ...

8. go.drugbank.com go.drugbank.com/drugs/DB01184

Domperidone: Uses, Interactions, Mechanism of Action Domperidone is a dopamine receptor antagonist used as a peristaltic stimulant and anti-emetic agent for dyspepsia, indigestion, epigastric pain, nausea, and ...

9. dhpp.hpfb-dgpsa.ca dhpp.hpfb-dgpsa.ca/review-documents/resource/SSR1691692252806

Summary Safety Review - Domperidone Domperidone is a prescription drug authorized for sale in Canada to treat symptoms of slowed stomach emptying seen with certain gastrointestinal disorders, and ...