|- candidate number||29464|
|- NTR Number||NTR7449|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||27-aug-2018|
|- Secondary IDs||2017-003766-27 NL63470.029.17|
|- Public Title||Amitriptyline en mirtazapine bij langdurige slapeloosheid|
|- Scientific Title||The DREAMING study: Efficacy of low dose amitriptyline or mirtazapine for insomnia disorder: a double-blind, randomized, placebo-controlled trial in general practice. |
|- hypothesis||Compared to placebo treatment with low dose amitriptyline or mirtazapine during 16 weeks will improve subjective insomnia in insomnia disorder patients in general practice.|
|- Healt Condition(s) or Problem(s) studied||Insomnia, Sleepproblems|
|- Inclusion criteria||- Adults aged 18-85 years and registered as patient with one of the participating general practices in the Netherlands. |
- Presence of insomnia disorder conform DSM-5, i.e. sleep problems (including problems maintaining sleep) in at least 3 nights a week during at least 3 months, with consequences for daytime functioning.
- Request for long-term and/or frequent sleep medication put to their GP because non-pharmacological treatment according to the Dutch (NHG) general practice guideline is deemed insufficient by both patient and GP.
|- Exclusion criteria||General exclusion criteria |
- Isolated problem falling asleep (without problems maintaining sleep).
- Insomnia secondary to another medical condition, e.g. OSAS, comorbid major depression, chronic pain.
- Habitual shift worker doing night shifts.
- Wish to continue (over-the-counter) products containing melatonin / cannabis.
- Use of off-label amitriptyline or mirtazapine for insomnia in the past year.
- Terminal illness.
- Suicide risk.
- Pregnancy, lactation or wish to become pregnant in the coming 6 months.
- Vulnerability due to unstable health situation according to GP.
- Being unable to follow study instructions and fill out the study questionnaires (in Dutch).
- Participation in other interventional medical scientific studies.
- Allergy for amitriptyline or mirtazapine.
- Cardiac arrhythmia / blockade / Long QT syndrome / Brugada syndrome / Family history of acute cardiac death.
- Recent myocardial infarction (within the past 90 days) / Angina pectoris / coronary insufficiency.
- Severe renal insufficiency (GFR < 10).
- Severe liver dysfunction.
- Ocular Hypertension / Glaucoma.
- Bipolar affective disorder.
- Current alcohol or drug abuse/addiction.
Potential drug-drug interactions
- Current use of psychopharmaceuticals (including anxiolytics as e.g. benzodiazepines, antidepressants including St John’s wort and, anticonvulsants).
- Current use of antimycotics (all types).
- Certain enzyme inductors, antiretroviral drugs, cimetidine and clonidine. (All of these are not commonly used and will be excluded by the prescription check by the GP and/or the final check by the pharmacist).
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||15-nov-2018|
|- planned closingdate||15-mei-2020|
|- Target number of participants||156|
|- Interventions||The investigational treatment, on top off usual care, consists of one tablet of amitriptyline (10 mg) or mirtazapine (7.5 mg) or an identical appearing placebo per night during 16 weeks. During treatment, participants visit their GP at least twice ( at week 3 and week 14) to evaluate their sleep and treatment satisfaction. In addition, at 3 weeks GP and participant can opt to double the dosage (2 units per night). At 14 weeks the GP and participant talk through stopping the trial medication at 16 weeks in case of single dosages and in case of double dosages, lowering from double to single dosage from 14 weeks onwards and stopping treatment at 16 weeks. During treatment and follow-up, care as usual of the participant’s GP continues, without restrictions. |
|- Primary outcome||The primary outcome of the study is the insomnia severity as measured by the Insomnia Severity Index (ISI) (Morin e.a. 2011). The ISI is a 7-item questionnaire scored on a 5-point Likert scale reflecting the severity of both nighttime and daytime aspects of insomnia disorder as perceived by the participant in the last 2 weeks with scores ranging from 0 (no insomnia) to 28 (severe insomnia). The ISI is the recommended outcome measure in insomnia trials (Buysse e.a. 2006) and is a valid and reliable instrument as an outcome measurement (ref). It possesses adequate internal consistency and is sensitive to changes in perceived sleep difficulties over time (Bastien e.a. 2001; Morin e.a. 2011). The total score can be interpreted as follows: absence of insomnia (0–7); sub-threshold insomnia (8–14); moderate insomnia (15–21); and severe insomnia (22–28) (Morin e.a. 2011). Insomnia will be evaluated at each time point: baseline, 6 weeks, 12 weeks, 20 weeks and 12 months.|
|- Secondary outcome||Secondary outcomes include subjective sleep quality quantified by sleep indices (Sleep Diary, PSQI items, Global rate of change), daytime functioning (WSAS, GSII), daytime symptoms as fatigue, (MFI, Flinders Fatigue Scale items), anxiety and depression (HADS). , safety and treatment evaluation (side effects (ASEC), withdrawal symptoms (DESS), treatment satisfaction and adherence (MARS as well as self-composed, study specific questions). Treatment adherence will also be assessed by pill count. Care consumption is based on self-report and medical records in general practice.
|- Timepoints||baseline, 6 weeks, 12 weeks, 20 weeks, 52 weeks. |
|- Trial web site|
|- CONTACT FOR PUBLIC QUERIES|| Mette Bakker |
|- CONTACT for SCIENTIFIC QUERIES|| Mette Bakker |
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|- Brief summary||Although non-pharmacological treatment is first choice, insomnia disorder patients often request at some point concomitant sleep medication. Clinical experience suggests that low dose sedating antidepressants might be effective. General practitioners increasingly prescribe off label amitriptyline and mirtazapine to promote sleep maintenance. However, controlled-data to support this off label prescription practice is lacking. This study aims to investigate the efficacy of treatment with amitriptyline (10-20mg) and mirtazapine (7,5-15mg) during 16 weeks compared to placebo for insomnia disorder in general practice. |
|- Main changes (audit trail)|
|- RECORD||27-aug-2018 - 3-okt-2018|