Study of Ondansetron in the Prevention of Sleep Syncope: The Nineth Prevention of Syncope Trial (POST9)

NCT05657925 | Not Yet Recruiting Phase 3

• 1 other identifier: POST9
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

At least 5% of patients with vasovagal syncope also have Sleep Syncope. Patients awake from sleep with profound malaise and gastrointestinal vagal symptoms. About 75% have severe nausea and about 40% have lower abdominal cramps. Some faint while supine, but most find their symptoms so severe that they rise quickly and hurry to the bathroom. Sometime either on the way to the toilet, near it, or shortly afterwards they faint. The nausea is followed by vomiting, and the cramps by watery diarrhea. After relief the patients remain presyncopal, diaphoretic, and tired. Almost all patients also have clinical vasovagal syncope during daytime hours. The cause of this is unknown. Orthostatic stress cannot be a factor in triggering the event, and in isolated case reports it occurs during non-REM sleep. There is no classic provocative situation of pain, the sight of trauma, or the presence of medical settings. These suggest the importance of central processes and the reduced likelihood that strategies that target maintaining preload (such as with midodrine and fludrocortisone) would be helpful. As well, midodrine is avoided during the night. Recently the investigators reasoned that if the investigators could rapidly suppress the nausea patients could remain supine, wait out the nausea, and not faint with orthostatic stress. Ondansetron is a potent anti-nausea medication that has rapidly dissolving preparations. Nine patients were instructed to keep one at the bedside, insert it upon waking up with nausea, remain in bed, and raise their legs (if possible). There was partial success with ondansetron 4 mg and complete success with ondansetron 8 mg. This remarkable but anecdotal observation requires formal testing. Research Objectives: the investigators will test the hypothesis that ondansetron 8 mg prn sublingually on awakening with moderate to severe nausea prevents loss of consciousness in patients with prior Sleep Syncope who awaken with malaise and nausea. Study Design \& Methodology: The main study will be a placebo-controlled, double-blind, randomized, crossover clinical trial. 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 of either ondansetron 8 mg sublingual tablets or matching placebo. They will each receive 3 boxes of 10 tabs, with refills available if needed. Each crossover period will last 6 months. In a substudy the investigators will test whether the predominant disturbed physiology is bradycardia, decreased venous return, or decreased systemic vascular resistance. This will be assessed using a unique, small, wearable blood pressure sensor that can be rapidly donned on the ear. It records heart rate and beat-to-beat waveforms, which permit estimating stroke volume, systemic vascular resistance, and cardiac output. the investigators will record these variables in all patients continuously from when the device is put on until 30 minutes afterwards. the investigators hypothesize that unlike during syncope provoked by head-up tilt testing, here there will be no decrease in preload until patients arise, and that the main physiologic disturbance during syncope is hypotension due to decreased preload superimposed on heart rate collapse. Anticipated Outcomes: If successful, this research would be i) the first to report a well-tolerated and highly effective treatment for most sleep syncope, and ii) the first to report the physiology of brain-initiated vasovagal syncope in the community outside a laboratory environment.

Conditions

Sleep Syncope

Keywords

Ondansetron

Outcome Measures

Primary Outcomes (1)

• nausea event causing the patient to awake and prevented from progressing to syncope

  One nausea event causing the patient to awake and prevented from progressing to syncope

  Within 12 months period of the study

Secondary Outcomes (6)

• In a substudy we will test whether the predominant disturbed physiology is bradycardia, decreased venous return, or decreased systemic vascular resistance

  Within 12 months period of the study

• Hospital Anxiety and Depression Scale (HADS)

  every 6 months of the study up to 12 months

• Generalized Anxiety Disorder score

  every 6 months of the study up to 12 months

• EQ-5D-3L

  every 6 months of the study up to 12 months

• Impact of Syncope on Quality of Life

  every 6 months of the study up to 12 months

Study Arms (2)

Ondansetron

ACTIVE COMPARATOR

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

Drug: ondansetron 8 mg

Placebo

PLACEBO COMPARATOR

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

Drug: Matching placebo

Interventions

ondansetron 8 mg DRUG

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

Ondansetron

Matching placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Syncope according to the American College of Cardiology Guidelines 2017
• ≥1 Sleep Syncope in the year preceding enrolment
• ≥-2 points on the Calgary Syncope Symptom Score for Structurally Normal Hearts
• Age ≥ 18 years with informed consent.

You may not qualify if:

• An inability to give informed consent
• pregnancy,
• unwilling or unable to use adequate birth control while on study drug
• QT interval exceeding 500 ms in the absence of correctable factors.

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

Location

MeSH Terms

Interventions

Ondansetron

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2022
• First Posted: December 20, 2022
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)