A Phase 3 interventional study of Atomoxetine Hydrochloride and Placebo in Vasovagal Syncope, sponsored by University of Calgary. Recruiting at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-05-09.
Sponsored by University of Calgary · Phase 3, Interventional, and Treatment
Among 15 studies in Syncope, Vasovagal with a site in Canada — 7 open to participants now, 9 under way, 1 of them phase 3. Syncope, Vasovagal · Canada.
Among the 15 studies in Syncope, Vasovagal with a site in Canada, this one is the 5th largest by planned enrollment of the 14 interventional ones, is one of 3 that started in 2022, is the only one in phase 3, and was the 9th registered.
88 studies on the registry are indexed under Syncope, Vasovagal; 28 are open to participants now.
This study's planned enrollment of 180 is above the median of 59 across 58 interventional studies indexed under Syncope, Vasovagal.
Browse Syncope, Vasovagal studies →7 of the 15 studies in Syncope, Vasovagal with a site in Canada are open now, in 1 country. Each count lists the studies.
Of the 24 Syncope, Vasovagal studies recruiting now, 13 (54%) set no upper age limit and 8 (33%) stop at 75 or younger; 6 take children under 18; 2 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →15 studies; the count open now beside each. This study's row is marked.
First in 2003; this study’s year is marked. 3 started in 2022.
Median enrollment 74 across the 14 interventional studies, 200 across the 1 observational. Of the 5 that completed or were terminated, 3 (60%) have results posted.
1 of 15 have an industry lead sponsor. The 8 most frequent:
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.
University of Calgary has 6 studies filed under Syncope, Vasovagal — fewer than ten, so there is no comparison to draw.
5 of the studies in Syncope, Vasovagal with a site in Canada that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06336031Simon Fraser UniversityImpact of Blood Phobia on Fainting Susceptibility | 2026-12 |
| NCT03446326University of CalgaryAssessment of Stroke Volume and Cardiac Output in Response to Varying Heart Rates | 2027-01-01 |
| NCT05621460Simon Fraser UniversityThe Effect of Water Carbonation on Orthostatic Tolerance | 2027-04 |
| NCT05633693Simon Fraser UniversityPostural Sway and Counterpressure Maneuvers for Pediatric Syncope | 2027-05 |
| NCT05555771Dr. Victoria ClaydonPaediatric Syncope in the Emergency Department | 2027-09-30 |
Among the 15 studies in Syncope, Vasovagal with a site in Canada, from their registry updates:
Nothing recorded among them since 2026-09-25.
Project rationale: Vasovagal syncope (VVS) affects up to 50% of people, and recurrent syncope markedly reduces quality of life. We recently reported that it is frequently associated with injury and not surprisingly with clinical anxiety. Although conservative measures help many patients there remain many who require more care. CIHR-funded studies have shown that fludrocortisone and midodrine are effective but cannot be used in patients with contraindications such as hypertension and heart failure. Pacemakers are partially effective in older patients, but this is established only in the small minority with proven asystole. There remains a need for a simple, once-daily medication with few contraindications that can be used as first-line therapy for most patients with recurrent vasovagal syncope.
Preliminary Studies: Norepinephrine transport (NET) inhibitors show promise as a novel treatment. Three (reboxetine, sibutramine, and atomoxetine) all prevent vasovagal syncope in healthy subjects and vasovagal syncope patients on tilt tests. Atomoxetine, approved to treat attention deficit disorder, is a highly selective NET inhibitor. We reported a proof-of-principle, randomized, placebo-controlled trial of the efficacy of atomoxetine to prevent vasovagal syncope on tilt table tests. Patients underwent tilt testing after receiving either atomoxetine 40 mg or placebo. Fewer VVS patients fainted with atomoxetine than placebo (10/29 vs. 19/27; odds ratio 0.22, p \< 0.01). Our meta-analysis of the effects of NET inhibition on the vasovagal reflex induced by tilt tests was highly positive. A pre-post study showed that sibutramine reduced syncope frequency in highly symptomatic and drug-refractory patients. A similar pre-post study showed that atomoxetine also reduces syncope frequency about 85% in patients with frequent and drug-intolerant or drug-resistant vasovagal syncope. Therefore,NET inhibition by atomoxetine merits assessment based on positive proof-of-principle studies, an apparent class effect, and two open-label pre-post studies. These results provide the rationale for a formal randomized, placebo-controlled, crossover trial of atomoxetine in moderate-to-high risk patients with VVS.
Hypothesis: We will test the hypothesis that oral atomoxetine prevents syncope in patients with recurrent VVS.
The Study: Patients will be included based on a positive Calgary Syncope Symptom Score and a history of at least 2 faints in the previous year. Eligible patients will be randomized to atomoxetine 40 mg po twice daily or matching placebo in a randomized, placebo-controlled, parallel design, double-blind, crossover trial. Each arm will last 6 months with a 1-week washout period. The primary outcome measure will be the proportion of patients with at least 1 syncope recurrence. The study will be powered to detect a beneficial odds ratio of 0.5, selected on the basis of the control outcome rates in 2 similarly designed, previous studies and international expert requirements for effect size. A sample size of 180 subjects will provide 85% power of detecting a difference between the arms at p\<0.05. We will assess the effects of atomoxetine on quality of life, anxiety, injury, and the cost-effectiveness of atomoxetine treatment, and the effects of genetic factors on outcomes.
Substudies : The quality of life scales will be the SF-36 and the Euroqol EQ5D, which will also be used as the health utility index for the economic studies. The depression and anxiety scales will be the Hospital and Anxiety Depression Score (HADS) and the General Anxiety Disorder - 7 Score (GAD-7). Clinical anxiety is highly prevalent in patients with recurrent syncope. Injury will be self-reported using our published definitions. The health economic substudy will be from the health system perspective and will use Alberta administrative data. DNA will be collected from spit acquired in the Oragene saliva self-collection kits, and an initial candidate gene study might include alleles of CYP2D6, COMT, the serotonin (SLC6A4) and norepinephrine (SLC6A2) reuptake transporters, and the 5HT1A and 5HT3 receptors.
Summary: Adults who faint recurrently are highly symptomatic. There are no therapies suitable for most patients have withstood the test of randomized clinical trials. If successful, atomoxetine will reduce syncope and improve quality of life.
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.
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.
Atomoxetine 40 mg PO BID (morning and late afternoon) Dosing will start at 40 mg daily for 3 days1 week, followed by a forced titration to 40 mg BID, as per the FDA label for atomoxetine.
Drug: Atomoxetine Hydrochloride
Matching placebo will be identical in appearance to the active treatment pill. BID (morning and late afternoon)
Drug: Placebo
Atomoxetine 40 mg PO BID (morning and late afternoon) Dosing will start at 40 mg daily for 3 days1 week, followed by a forced titration to 40 mg BID, as per the FDA label for atomoxetine
Placebo Comparator: Placebo Matching placebo will be identical in appearance to the active treatment pill. BID (morning and late afternoon)
The primary outcome measure will be the proportion of patients having at least one syncope recurrence.
one syncope recurrence
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
Rand 36 Scale
The RAND 36-Item Health Survey (Version 1.0) taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible. Aggregate scores are compiled as a percentage of the total points possible, using the RAND scoring table
Time frame: every 6 months of the study up to 12 months
ISQL form
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
Medical Utilization form
Cost, and cost-effectiveness
Time frame: every 3 months of the study up to 12 months
Plan to share: No
No publications or documents are linked to this record.
Started Jun 2022 (actual). Primary completion is estimated for Sep 2026, 51 months after the start.
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Studies of the drug tested here: Atomoxetine