Overview
Sponsor-declared trial summary
Phase
Phase III and Phase IV (Integrated)
Status
Ended
Participants planned
190
Countries
1
Sites
1
insomnia
The main objective of the study is to determine whether low dose amitriptyline (10-20 mg) in chronic insomnia coexisting with medical conditions is as effective as CBT-I in improving subjective sleep.
Key facts
- Sponsor
- Ziekenhuis Gelderse Vallei Stichting
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Psychiatry and Psychology [F] - Psychological Phenomena [F02]
- Trial duration
- 29 Oct 2024 → 14 Jan 2026
- Decision date (initial)
- 2024-10-29
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Ziekenhuis Gelderse Vallei
External identifiers
- EU CT number
- 2024-518320-71-00
- EudraCT number
- 2019-001520-35
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy
The main objective of the study is to determine whether low dose amitriptyline (10-20 mg) in chronic insomnia coexisting with medical conditions is as effective as CBT-I in improving subjective sleep.
Secondary objectives 4
- Investigating the long-term efficacy of amitriptyline in comparison to CBT-I.
- Determining the effect of amitriptyline in comparison to CBT-I on daytime symptoms and functioning.
- Determining whether the medication is well tolerated (safe)
- Identifying mediators and moderators of treatment outcome.
Conditions and MedDRA coding
insomnia
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Treatment 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.
|
Randomised Controlled | None | Amitriptyline: One or two units (tablets) of amitriptyline (10 mg/tablet) during 12 weeks Cognitive behavioural therapy (CBT-I): The treatment regime of the cognitive behavioural therapy (CBT-I) consists of 6 weekly group session and a follow up session with a psychologist at 12 weeks. |
|
| 2 | Follow up Participants who respond to the treatment are followed up to 12 months post treatment
until relapse.
|
Not Applicable | None |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Adults aged 18 - 85 years 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 or more on the lnsomnia Severity lndex (lSl)
- Have a medical condition and/or chronic pain (> 3 months).
Exclusion criteria 23
- 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
- Presence of a severe psychiatric disorder not in remission or adequately treated
- Current alcohol or drug abuse or addiction (benzodiazepine excluded)
- Participation in other interventional medical scientific studies
- Current use of psychopharmaceuticals other than benzodiazepines
- 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) and/or severe liver dysfunction
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The mean subjective insomnia severity score, measured by the insomnia severity index (ISI) at 12 weeks
Secondary endpoints 3
- Sleep quality quantified by sleep efficiency (by sleep diary)
- Daytime functioning and symptoms (fatigue, emotional complaints, physical functioning, impairment of functioning).
- Adverse events and treatment evaluation (side effects, withdrawal symptoms, and adherence)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Amitriptyline HCl CF 10 mg, filmomhulde tabletten
PRD394076 · Product
- Active substance
- Amitriptyline Hydrochloride
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 1470 mg milligram(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- N06AA09 — AMITRIPTYLINE
- Marketing authorisation
- RVG 52947
- MA holder
- CENTRAFARM B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Ziekenhuis Gelderse Vallei Stichting
- Sponsor organisation
- Ziekenhuis Gelderse Vallei Stichting
- Address
- Willy Brandtlaan 10
- City
- Ede Gld
- Postcode
- 6716 RP
- Country
- Netherlands
Scientific contact point
- Organisation
- Ziekenhuis Gelderse Vallei Stichting
- Contact name
- Nynke Rauwerda
Public contact point
- Organisation
- Ziekenhuis Gelderse Vallei Stichting
- Contact name
- Nynke Rauwerda
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ended | 190 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Ziekenhuis Gelderse Vallei Stichting
Medical Psychology, Willy Brandtlaan 10, 6716 RP, Ede Gld
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2024-10-29 | 2026-01-14 | 2024-10-29 | 2024-10-29 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| Summary of results primary and secondary outcome at 12 weeks treatment SUM-127426
|
2026-04-02T18:02:10 | Submitted | Summary of Results |
Documents 5 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-518320-71-00 | 4.3 |
| Recruitment arrangements (for publication) | K1_Blank document_ Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 2024-518320-71-00 | 6 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC amitriptyline | 1 |
| Summary of results (for publication) | Summary study results TIMELAPSE study | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-07 | Netherlands | Acceptable 2024-10-29
|
2024-10-29 |