This study has been transitioned to CTIS with ID 2024-518320-71-00 check the CTIS register for the current data. The main objective of the study is to determine whether low dose amitriptyline (10-20 mg nightly) in chronic insomnia coexisting with…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
insomnia stoornis
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the mean subjective insomnia severity score,
measured by the insomnia severity index (ISI). Primary endpoint is at 12 weeks.
Secondary outcome
During the follow-up period maintenance of the treatment response assessed
operationalized as having a >= 8 point reduction on the ISI Secondary
outcomes include sleep quality quantified by sleep efficiency, questionnaires
on daytime functioning and symptoms (fatigue, emotional complaints, physical
functioning impairment of functioning). Possible moderators are type of
insomnia, dysfunctional attitudes and beliefs about sleep, pre sleep arousal.
Furthermore adverse events and treatment evaluation (side effects, withdrawal
symptoms, and adherence) are assessed.
Background summary
Insomnia is common in people with medical conditions. Insomnia is related to
increased mortality and morbidity. Cognitive behavioral therapy for insomnia
(CBT-I) is first choice of treatment and also effective for people with
insomnia and medical conditions. In general CBT-I does not lose its
effectiveness when delivered in a less costly format as a group therapy.
Despite the evidence that CBT-I is an effective intervention, there can be
limitations to CBT-I for patients with medical conditions, requiring a safe
alternative.. Preliminary evidence and clinical experience suggests that
off-label low dose use of sedating antidepressants such as amitriptyline (AM),
might be non-addictive, effective, and well-tolerated alternative to treat
insomnia in patients with medical comorbidity.
Study objective
This study has been transitioned to CTIS with ID 2024-518320-71-00 check the CTIS register for the current data.
The main objective of the study is to determine whether low dose amitriptyline
(10-20 mg nightly) in chronic insomnia coexisting with medical conditions is as
effective as CBT-I in improving subjective sleep.
Secondary objectives include (1) investigating the long-term efficacy of
amitriptyline in comparison to CBT-I, (2) determining the effect on daytime
symptoms and functioning, (3) determining whether the medication is well
tolerated (safe) (4) identifying mediators and moderators of treatment outcome.
Study design
The study is a non-inferiority randomized controlled trial. Participants
(n=2*9584) will complete clinical assessments and then will be randomly
assigned to (1) Cognitive behavioral therapy (CBT-I), (2) amitriptyline for 12
weeks (AM). Outcomes will be assessed at baseline and after 12 weeks. All
treatment responders will be assessed for a period of maximal 12 months after
treatment. The score on the Insomnia Severity Index (ISI), a patient-reported
outcome, will serve as the primary endpoint for treatment comparisons. All
treatment responders will be assessed for a period of maximal 12 months after
treatment. Treatment responders are defined as having >= 8 point reduction on
ISI (Morin e.a. 2011). Data will be gathered on secondary outcomes, baseline
characteristics, and possible moderators and mediators. In both conditions
adherence, side effects are assessed and withdrawal in the medication
condition.
Intervention
Participants are treated during 12 weeks with either amitriptyline (starting
with 10 mg per day, respectively, and, if ineffective, possible doubling of
this dose after 3 weeks, and stopping after 12 weeks) or cognitive behavioural
therapy 6 weekly sessions and a follow up session after 6 weeks, followed by
usual care by their neurologist-somnologist. Follow up will continue until 12
months after treatment.
Study burden and risks
10 assessments will take place: at baseline, at start treatment, 6, 12 and 14
weeks, and the responders during follow-up (i.e. reduction on ISI <8 until
relapse) at 2, 4, 6 , 8 , 10 and 12 months post treatment. A one-week sleep
diary is requested at start treatment,12 weeks, and 12 months post treatment.
During treatment, patients visit their neurologist at least once. No major
health risks are expected for participants in the medication condition, given
the level of clinical experience with these antidepressants that are generally
well-tolerated, the low dosage in this study, and the exclusion of risk groups.
The medication intervention group may benefit from the intervention by improved
quality of their sleep and may experience mild reversible side effects. The
CBT-I group will benefit by receiving the treatment of first choice. Both
groups will benefit from the frequent monitoring (post) treatment and
possibility to get access to the other treatment option, when insomnia does not
improve or remits after treatment. Both approval or rejection of the hypothesis
lead to an evidence based clinical guideline on the use of amitriptyline.
Willy Brandtlaan 10
Ede 6716 RP
NL
Willy Brandtlaan 10
Ede 6716 RP
NL
Listed location countries
Age
Inclusion criteria
- Adults aged 18 - 85 years and older visiting the outpatient clinic department
of neurology.
- Presence of insomnia disorder conform DSM-5, i.e. sleep problems in at least
3 nights a week, for at least 3 months with consequences for daytime
functioning, the sleep problem cannot be better explained by or occurs
exclusively during the course of another sleep disorder (e.g. sleep related
breathing disorder, parasomnia)
- Score of >=10 on the Insomnia Severity Index (ISI)
- Have a medical condition and / or chronic pain (> 3 months).
Exclusion criteria
- Habitual night shift worker
- Untreated sleep related breathing disorder
- Wish to continue over-the-counter sleep aids as melatonin and medicinal
cannabis
- Use of off-label amitriptyline for insomnia in the past year
- Being unable to follow study instructions and fill out the study
questionnaires (in Dutch)
- A known diagnosis of dementia
- History of delirium
- Pregnancy, lactation or wish to become pregnant in the coming 6 months
- Terminal illness (prognosis < 1 year)
- Suicide risk
- Epilepsy
- Ocular Hypertension / Glaucoma
- The presence of a severe psychiatric disorder not in remission or adequately
treated.
- Current alcohol or drug abuse/addiction (benzodiazepine excluded).
- Participation in other interventional medical scientific studies
- Current use of psychopharmaceuticals other than benzodiazepine (
antidepressants including St John*s wort, anticonvulsants)
- Current use of antimycotica
- Allergy for amitriptyline
- 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-518320-71-00 |
| EudraCT | EUCTR2019-001520-35-NL |
| CCMO | NL68611.018.19 |