Ondansetron for Sleep Fainting

(POST9 Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Calgary

Must be taking: Ondansetron

Disqualifiers: Pregnancy, QT interval > 500 ms, others

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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 14

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether ondansetron can prevent fainting episodes in individuals with Sleep Syncope, a condition where people wake up extremely nauseous and may faint while rushing to the bathroom. Ondansetron, an anti-nausea drug, is taken sublingually (dissolved under the tongue) upon waking with nausea. Participants will receive either ondansetron tablets or a placebo to determine if the medication can stop fainting spells. Those who frequently wake up feeling very nauseous and have fainted in the past year may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that ondansetron, the treatment being tested, is generally safe for people. It already has approval for other uses in several countries. However, some possible side effects are important to note. Studies have found that ondansetron can affect heart rhythms, potentially causing fainting or lightheadedness. Report any changes in heartbeat or unusual dizziness to your healthcare team. Despite these risks, many people tolerate ondansetron well when used correctly. ^{1 2 3 4 5}

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

Ondansetron is unique because it targets nausea, which is a key trigger for sleep fainting, using an effective and established anti-nausea mechanism. Unlike the typical treatments for sleep fainting that might focus on cardiovascular or neurological factors, ondansetron works by blocking serotonin receptors in the brain that are linked to nausea and vomiting. Researchers are excited about this treatment because it offers a novel approach by addressing the nausea component directly and can be administered sublingually, potentially providing rapid relief when symptoms arise.

What evidence suggests that ondansetron might be an effective treatment for sleep syncope?

Research has shown that ondansetron, a medication used to prevent nausea, might help stop fainting episodes by quickly easing nausea. In this trial, participants in one arm will receive ondansetron 8 mg sublingually upon awakening with nausea. Some patients have reported that taking ondansetron in this manner completely relieved their symptoms, allowing them to stay in bed and avoid fainting. Additionally, studies have found that ondansetron can lower the risk of low blood pressure, which is often linked to fainting. This suggests that ondansetron could help people who feel nauseous and unwell when they wake up, preventing them from fainting. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults over 18 who experience fainting during sleep and meet certain criteria for vasovagal syncope. They must have had at least one such episode in the past year and score a specific minimum on a syncope symptom scale. Pregnant individuals, those unable to consent, or not using birth control, as well as anyone with a long QT interval on an ECG are excluded.

Inclusion Criteria

You have experienced fainting as outlined in the American College of Cardiology Guidelines from 2017.

You have a Calgary Syncope Symptom Score of at least -2 for structurally normal hearts.

I have fainted during sleep at least once in the last year.

Exclusion Criteria

Your heart's QT interval is longer than 500 milliseconds without any fixable reasons.

I am unable to understand and agree to the study's details on my own.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either ondansetron 8 mg sublingual tablets or matching placebo upon awakening with nausea

6 months

Visits at baseline, 3 months, and 6 months

Crossover

Participants switch from one treatment arm to the other

6 months

Visits at 9 months and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ondansetron

Trial Overview The study tests if Ondansetron (an anti-nausea medication) can prevent fainting when taken sublingually upon waking with nausea due to Sleep Syncope. It's compared against a placebo in a double-blind crossover design where participants switch between treatments after six months.

How Is the Trial Designed?

Group I: Ondansetron Active Control 1 Intervention

ondansetron 8 mg prn sublingually when awakening with nausea. as per the FDA label for ondansetron.

Group II: Placebo Placebo Group 1 Intervention

Matching placebo will be identical in appearance to the active treatment pill.

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?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Published Research Related to This Trial

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]

Ondansetron is highly effective in treating acute nausea and vomiting, outperforming metoclopramide, and shows minimal toxicity, making it particularly beneficial for young patients.

While ondansetron demonstrates consistent effectiveness in non-cisplatin and radiotherapy settings, its efficacy in cisplatin-related delayed emesis remains uncertain, highlighting the importance of patient preferences in choosing anti-emetic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introduction: the clinical challenge. Schmoll, HJ.[2013]

In a pilot study of 20 patients with acute unilateral vestibular neuritis, ondansetron treatment resulted in a significantly lower early caloric vestibular deficit compared to metoclopramide, suggesting it may be more effective in managing vestibular symptoms.

Patients receiving ondansetron also experienced shorter hospital stays and quicker times to independent walking, indicating that it not only helps with symptoms but may also improve recovery times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A protective effect of 5-HT3 antagonist against vestibular deficit? Metoclopramide versus ondansetron at the early stage of vestibular neuritis: a pilot study. Venail, F., Biboulet, R., Mondain, M., et al.[2014]

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]

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, administered intravenously at 4 mg once daily for 3-5 days, effectively controlled nausea in 59% and emesis in 68% of patients receiving non-platinum anticancer drugs, demonstrating its efficacy as an anti-emetic.

The safety profile of Ondansetron was strong, with 98% of cases showing no safety issues, and only minor side effects like headache and constipation reported in a few instances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Examination of anti-emetic effect and safety of multiple intravenous doses of ondansetron in patients receiving nonplatinum anti-cancer drugs]. Nukariya, N., Niitani, H., Taguchi, T., et al.[2013]

Citations

1. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05657925/study-of-ondansetron-in-the-prevention-of-sleep-syncope-the-nineth-prevention-of-syncope-trial-post9

Study of Ondansetron in the Prevention of Sleep Syncope The primary outcome will be the progression of awakening with nausea to syncope. Thirty patients with Sleep Syncope will be randomized 1:1 to ...

2. withpower.com withpower.com/trial/phase-3-syncope-1-2023-b23df

Ondansetron for Sleep Fainting · Info for Participants The primary outcome will be the progression of awakening with nausea to syncope. Thirty patients with Sleep Syncope will be randomized 1:1 to receive packages ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05755737

NCT05755737 | A Proof of Principle Study of Ondansetron ... About 20% of adults faint recurrently. These patients are often highly symptomatic, have problems with employment and driving, can be injured, and have poor ...

4. mdpi.com mdpi.com/1424-8247/15/12/1588

Ondansetron Reduces the Incidence of Hypotension after ... Our meta-analysis of 25 RCTs revealed that ondansetron can significantly reduce the risks of hypotension (NNT 7.5) and bradycardia (NNT 16.7), ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11247051/

The effects of ondansetron on sleep-disordered breathing in ... Ondansetron significantly reduced the respiratory disturbance index (RDI) in REM sleep from 24.15+/-4.85 events/hour at placebo to 11.01+/-1.56 events/hour with ...

6. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-abnormal-heart-rhythms-may-be-associated-use-zofran-ondansetron

Abnormal heart rhythms may be associated with use of ... Ondansetron may increase the risk of developing abnormal changes in the electrical activity of the heart, which can result in a potentially fatal abnormal ...

7. goodrx.com goodrx.com/zofran/worst-zofran-side-effects?srsltid=AfmBOoqjfBvUtj9vkZ5No91DijWm__VoXPcx74KMEI3IhCTMKnyPb5aQ

7 Zofran Side Effects (and When to Seek Medical Care) Let your healthcare team know right away if you notice lightheadedness, changes in heart rate, or fainting spells while taking Zofran.

8. mayoclinic.org mayoclinic.org/drugs-supplements/ondansetron-injection-route/description/drg-20065221

Ondansetron (injection route) - Side effects & uses This medicine can cause changes in heart rhythms, including QT prolongation. It may change the way your heart beats and cause fainting or ...

9. drugs.com drugs.com/ondansetron.html

Ondansetron Uses, Dosage & Side Effects Yes, ondansetron (Zofran) might make you feel sleepy or tired. Ondansetron injection for the treatment of post-operative nausea and vomiting has ...