A Phase 3 interventional study of ondansetron 8 mg and Matching placebo in Sleep Syncope, sponsored by University of Calgary. Not yet recruiting at 1 site in Canada. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2024-05-09.
Sponsored by University of Calgary · Phase 3, Interventional, and Treatment
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.
Trial interventions: Randomization will be to ondansetron 8 mg sublingual tablets or matching placebo tablets kept at the bedside, to be used upon awakening with premonitory nausea. This is a commonly used dose for rapid treatment of nausea.
Randomization: Patients will be randomized into two treatment groups will be carried out centrally with a randomization scheme using a computerized algorithm. Medication containers will be filled and labelled with the randomization code number centrally. The investigators will complete a screening log of eligible but nonrandomized patients that will contain demographic data and the reason for non-randomization.
Followup: Study nurse coordinators will see the patients in clinic at baseline, 3 months, 6 months, 9 months, and 12 months. The 6-month visit will be the visit during which the patients will be crossed over from one arm to the other. The total study duration will be 52 weeks for each participant. Patients will be asked to notify the study nurse if they experience a premonitory nausea awakening either with or without an ensuing syncope. Pill counts will be conducted to confirm the number of events.
201 studies on the registry are indexed under Syncope; 36 are open to participants now.
This study's planned enrollment of 24 is below the median of 100 across 108 interventional studies indexed under Syncope.
Browse Syncope studies →University of Calgary is the lead sponsor of 703 studies on the registry; 196 are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 2 (20%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ondansetron 8 mg prn sublingually when awakening with nausea. as per the FDA label for ondansetron.
Drug: ondansetron 8 mg
Matching placebo will be identical in appearance to the active treatment pill.
Drug: Matching placebo
Ondansetron 8 mg prn sublingually when awakening with nausea. as per the FDA label for ondansetron.
Matching placebo will be identical in appearance to the active treatment pill
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
Time frame: Within 12 months period of the study
In a substudy we 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 donned rapidly on the ear.
Time frame: Within 12 months period of the study
Hospital Anxiety and Depression Scale (HADS)
The total score is out of 42, (21 per subscale). Scores are derived by summing responses for each of the two subscales or for the scale as a whole Higher scores indicate greater levels of anxiety or depression. The total HADS score may be regarded as a global measure of psychological distress
Time frame: every 6 months of the study up to 12 months
Generalized Anxiety Disorder score
The GAD-7 is useful in primary care and mental health settings as a screening tool and symptom severity measure for the four most common anxiety disorders (Generalized Anxiety Disorder, Panic Disorder, Social Phobia and PostTraumatic Stress Disorder). It is 70-90% sensitive and 80-90% specific across disorders / cutoffs (see Evidence section for more). Higher GAD-7 scores correlate with disability and functional impairment (in measures such as work productivity and health care utilization)
Time frame: every 6 months of the study up to 12 months
EQ-5D-3L
The EQ-5D-3L classification system consists of five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, each with three levels: no problems "1", moderate problems "2", and severe problems "3". Each health state is described as a vector of these five dimensions. With 3 levels for each dimension, the EQ-5D-3L describes 243 distinct health states, with 11111 being the best health state (full health), and 33333 the worst health state. In addition to the classification system, each of the instruments also includes a visual analogue scale (EQ VAS). The EQ VAS records the respondent's self-rated health on a visual analogue scale from 0 to 100, whereby 0 indicates 'the worst health you can imagine', and 100 'the best health you can imagine'. This information can be used as a quantitative measure of health as judged by the individual respondents.
Time frame: every 6 months of the study up to 12 months
Impact of Syncope on Quality of Life
The ISQL is a brief valid measure of the impact of syncope on quality of life. It measures impairment, fear, depression, and physical limitations, and correlates with recent syncope frequency.
Time frame: every 6 months of the study up to 12 months
The Short-Form (SF-36) Health Survey
The SF-36 is a multi-purpose survey designed to capture adult patients' perceptions of their own health and well-being.
Time frame: every 6 months of the study up to 12 months
Plan to share: No
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Studies of the drug tested here: Ondansetron