InsomniaPhase 3ALPHASOMNCT02139098
Alternative Dosing Regimens in the Pharmacotherapy of Insomnia
A Phase 3 study testing Amitriptyline and Zolpidem in people with Insomnia, run by Philipps University Marburg at 1 site in Germany.
Trial summary
The purpose of this study is to evaluate whether drug efficiency of zolpidem and amitriptyline can be conditioned according to learning theory in patients with primary insomnia. Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Insomnia
- What is being tested?
- Amitriptyline and Zolpidem
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteGermany
- Study dates
- May 2014to Nov 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age between 18 years to 69 years
- fluent in German language
- provide written informed consent
- ability to understand the explanations and instructions given by the study physician and the investigator
Who cannot join
- Sleep disorders caused by medical factors (e.g. sleep apnea, restless legs syndrome, narcolepsy, substance-induced insomnia)
- Contraindications to study medication intake according to the information sheet for health professionals (Summary of medicinal Product Characteristics, SmPC; Fachinformation in Germany) assessed by physical examination (including ECG) and medical history
- allergies to amitriptyline hydrochloride or any of its ingredients
- allergies to zolpidem or any of its ingredients
- acute intoxication with alcohol, analgetics, hypnotics or any other psychotropic drug
- urinary retention
Show all 32Show fewer
- delirium
- untreated closed-angle glaucoma
- prostatic hyperplasia
- pyloric stenosis
- paralytic ilius
- suicidal thoughts
- liver/ kidney/ pulmonary insufficiency
- myasthenia gravis
- hypokalemia
- bradycardia
- coronary heart disease, cardiac arrhythmias, long QT syndrome or other clinically relevant cardiac disorders
- increased risk of seizures/ history of seizures
- substance dependence syndrome/ history of substance dependence syndrome
- Allergies to ingredients of placebo or novel-tasting drink (CS)
- currently pregnant (verified by urine pregnancy test) or lactating
- patients scoring ≥12 on the Epworth Sleepiness Scale
- patients scoring below 8 or above 21 on the Insomnia Severity Index
- patients suffering from a mental disorder as verified by the SCID (major depression; psychosis; brain injury; substance abuse or dependency syndrome during the last 6 months before V1)
- nicotine consumption > 10 cigarettes/day
- unwillingness to refrain from alcohol consumption throughout the study
- Concomitant medication interfering with study medication intake due to potential interactions (all psychotropic medication including analgetics and muscle relaxants, hypericum derivatives; antihypertensives; anti-arrhythmic agents; antibiotics; cisaprid; anti-malaria drugs; diuretics; imidazole antifungals; cumarin derivatives; antihistaminics; calcium channel blockers; medications that enlarge the QT interval or may lead to hypokalemia)
- change in concomitant medication regime during the last 2 weeks prior to visit 1 or after randomization
- intake of psychotropic medication during the last 3 months
- participation in any other clinical trial 3 months prior to visit 1
- women of childbearing age not using 2 highly effective contraceptive methods
- employee of the Sponsor or the principal investigator
Trial locations and contacts
1 site in 1 country.
Germany1 site
Clinical Psychology and Psychotherapy, Department of Psychology, Philipps University Marburg
Marburg, Hesse, 35032
About this study
Official title: Phase III Study on Alternative Dosing Regimens in the Pharmacotherapy of Mild to Moderate Insomnia
The purpose of this study is to evaluate whether drug efficiency of zolpidem and amitriptyline can be conditioned according to learning theory in patients with primary insomnia.
Read the detailed description
Previous research has shown that repeated drug treatments can be regarded as conditioning processes. Sleep disorders are especially of interest to be investigated under the perspective of conditioning with drugs, since sleep quality can be defined both in terms of subjective ratings (self-rated sleep quality parameters) and objective measures (via polysomnographic assessment PSG; e.g., total sleep time, sleep onset, sleep architecture). By using two different drugs (zolpidem, amitriptyline) that modulate sleep differentially, the investigators intend to implement a conditioning paradigm in sleep disorders dissociating conditioning effects on subjective and objective sleep parameters. Both drugs should affect objective and subjective sleep parameters positively, while only amitriptyline should modulate the objectively assessed sleep architecture by REM-suppression (latency of REM-sleep onset, percentage of REM-sleep).Patients with mild to moderate insomnia will undergo a classical conditioning paradigm with one of two study medications: amitriptyline or zolpidem. After an acquisition period and a wash-out period, conditioned sleep changes are assessed in an evocation trial. During a second treatment phase of 7 days, patients receive different doses of amitriptyline (between 0mg and 50mg per night) or zolpidem (between 0mg and 5mg per night) to evaluate alternative dosing regimens in the pharmacotherapy of mild to moderate Insomnia.
- Conditions
- Insomnia
- Being tested
- Amitriptyline, Zolpidem, Placebo
- Keywords
- sleep architecture, conditioning of pharmacological responses, insomnia
- Medical subject headings
- Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmitriptylineDrug
50 mg capsule amitriptyline before going to bed on 8 out of 17 nights
ZolpidemDrug
5 mg capsule zolpidem before going to bed on 8 out of 17 nights
AmitriptylineDrug
50 mg capsule amitriptyline before going to bed on 13 out of 17 nights
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Amitriptyline flexible dosing | Experimental | 50 mg capsule amitriptyline before going to bed on 8 out of 17 nights/placebo Receives: Drug: Amitriptyline; Drug: Placebo |
| Zolpidem flexible dosing | Experimental | 5 mg capsule zolpidem before going to bed on 8 out of 17 nights/placebo Receives: Drug: Zolpidem; Drug: Placebo |
| Amitriptyline fixed dosing | Active comparator | 50 mg capsule amitriptyline before going to bed on 8 out of 17 nights Receives: Drug: Amitriptyline |
| Zolpidem fixed dosing | Active comparator | 5 mg capsule zolpidem before going to bed on 8 out of 17 nights Receives: Drug: Zolpidem |
| Amitriptyline continuous dosing | Active comparator | 50 mg capsule amitriptyline before going to bed on 13 out of 17 nights Receives: Drug: Amitriptyline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Total Sleep Time
assessed by polysomnography
Measured: Change from baseline to day 10 after first medication intake
Objective Sleep Onset Latency
assessed by polysomnography
Measured: Change from baseline to day 10 after first medication intake
Self-reported Total Sleep Time
assessed by sleep diary
Measured: Change from baseline to day 10 after first medication intake
Self-Reported Sleep Onset Latency
assessed by sleep diary
Measured: Change from baseline to day 10 after first medication intake
Secondary outcomes (7)
Percentage of REM sleep
assessed by polysomnography
Measured: Change from baseline to day 10 after first medication intake
REM onset latency
assessed by polysomnography
Measured: Change from baseline to day 10 after first medication intake
Objective Sleep Efficiency
assessed by actigraphy
Measured: Change from baseline to day 17 after first medication intake
Objective Total Sleep Time
assessed by actigraphy
Measured: Change from baseline to day 17 after first medication intake
Self-Reported Total Sleep Time
assessed by sleep diary
Measured: Change from baseline to day 18 after first medication intake
Self-reported Sleep Onset Latency (min)
assessed by sleep diary
Measured: Change from baseline to day 18 after first medication intake
Self-reported Sleep Onset Latency (evaluation)
assessed by sleep diary
Measured: Change from baseline to day 18 after first medication intake
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2014 (estimated)
- Study startMay 2014
- Primary completionNov 2017
- Study completionNov 2017
Why it stopped: Recruiting problems because of the time expenditure required for participating and the strict criteria of inclusion and exclusion
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InsomniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Philipps University Marburg
- Sponsor type
- University, hospital or other
- Collaborators
- Johannes Gutenberg University Mainz
- Responsible party
- Principal investigator, Winfried Rief, Philipps University Marburg
- Investigators
- Winfried Rief, Prof. Dr., Principal investigator, Clinical Psychology and Psychotherapy, Department of Psychology, Philipps University MarburgBettina K Doering, Dr., Principal investigator, Clinical Psychology and Psychotherapy, Department of Psychology, Philipps University MarburgCarmen Schade-Brittinger, Study chair, Koordinierungszentrum für Klinische Studien Marburg, Philipps University Marburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02139098
- Sponsor's protocol ID
- FOR1328-SP8
- Other IDs
- 2013-003229-27
- Acronym
- ALPHASOM
- Status last verified
- Mar 2018
- First submitted
- 24 Apr 2014
- Last updated
- 9 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study on Alternative Dosing Regimens in the Pharmacotherapy of Mild to Moderate Insomnia
- ClinicalTrials.gov ID
- NCT02139098
- Acronym / sponsor ID
- ALPHASOM / FOR1328-SP8
- Conditions
- Insomnia
- Keywords
- sleep architecture, conditioning of pharmacological responses, insomnia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruiting problems because of the time expenditure required for participating and the strict criteria of inclusion and exclusion
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Philipps University MarburgUniversity, hospital or other
- Collaborators
- Johannes Gutenberg University Mainz
- Study start
- May 2014
- Primary completion
- Nov 2017 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 15 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate whether drug efficiency of zolpidem and amitriptyline can be conditioned according to learning theory in patients with primary insomnia.
Detailed description
Previous research has shown that repeated drug treatments can be regarded as conditioning processes. Sleep disorders are especially of interest to be investigated under the perspective of conditioning with drugs, since sleep quality can be defined both in terms of subjective ratings (self-rated sleep quality parameters) and objective measures (via polysomnographic assessment PSG; e.g., total sleep time, sleep onset, sleep architecture). By using two different drugs (zolpidem, amitriptyline) that modulate sleep differentially, the investigators intend to implement a conditioning paradigm in sleep disorders dissociating conditioning effects on subjective and objective sleep parameters. Both drugs should affect objective and subjective sleep parameters positively, while only amitriptyline should modulate the objectively assessed sleep architecture by REM-suppression (latency of REM-sleep onset, percentage of REM-sleep).Patients with mild to moderate insomnia will undergo a classical conditioning paradigm with one of two study medications: amitriptyline or zolpidem. After an acquisition period and a wash-out period, conditioned sleep changes are assessed in an evocation trial. During a second treatment phase of 7 days, patients receive different doses of amitriptyline (between 0mg and 50mg per night) or zolpidem (between 0mg and 5mg per night) to evaluate alternative dosing regimens in the pharmacotherapy of mild to moderate Insomnia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Amitriptyline flexible dosing | Experimental | Drug: Amitriptyline, Drug: Placebo50 mg capsule amitriptyline before going to bed on 8 out of 17 nights/placebo |
| Zolpidem flexible dosing | Experimental | Drug: Zolpidem, Drug: Placebo5 mg capsule zolpidem before going to bed on 8 out of 17 nights/placebo |
| Amitriptyline fixed dosing | Active comparator | Drug: Amitriptyline50 mg capsule amitriptyline before going to bed on 8 out of 17 nights |
| Zolpidem fixed dosing | Active comparator | Drug: Zolpidem5 mg capsule zolpidem before going to bed on 8 out of 17 nights |
| Amitriptyline continuous dosing | Active comparator | Drug: Amitriptyline50 mg capsule amitriptyline before going to bed on 13 out of 17 nights |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- age between 18 years to 69 years
- fluent in German language
- provide written informed consent
- ability to understand the explanations and instructions given by the study physician and the investigator
Key exclusion criteria (32 listed)
- Sleep disorders caused by medical factors (e.g. sleep apnea, restless legs syndrome, narcolepsy, substance-induced insomnia)
- Contraindications to study medication intake according to the information sheet for health professionals (Summary of medicinal Product Characteristics, SmPC; Fachinformation in Germany) assessed by physical examination (including ECG) and medical history
- Allergies to ingredients of placebo or novel-tasting drink (CS)
- currently pregnant (verified by urine pregnancy test) or lactating
- patients scoring ≥12 on the Epworth Sleepiness Scale
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Amitriptyline50 mg capsule amitriptyline before going to bed on 8 out of 17 nights | Drug | Amitriptyline fixed dosing, Amitriptyline flexible dosing |
| Zolpidem5 mg capsule zolpidem before going to bed on 8 out of 17 nights | Drug | Zolpidem fixed dosing, Zolpidem flexible dosing |
| Amitriptyline50 mg capsule amitriptyline before going to bed on 13 out of 17 nights | Drug | Amitriptyline continuous dosing |
| PlaceboPlacebo | Drug | Amitriptyline flexible dosing, Zolpidem flexible dosing |
Primary outcome
Objective Total Sleep Time
Time frame: Change from baseline to day 10 after first medication intake
assessed by polysomnography
Objective Sleep Onset Latency
Time frame: Change from baseline to day 10 after first medication intake
assessed by polysomnography
Self-reported Total Sleep Time
Time frame: Change from baseline to day 10 after first medication intake
assessed by sleep diary
Self-Reported Sleep Onset Latency
Time frame: Change from baseline to day 10 after first medication intake
assessed by sleep diary
7 secondary outcomes
Percentage of REM sleep
Time frame: Change from baseline to day 10 after first medication intake
REM onset latency
Time frame: Change from baseline to day 10 after first medication intake
Objective Sleep Efficiency
Time frame: Change from baseline to day 17 after first medication intake
Objective Total Sleep Time
Time frame: Change from baseline to day 17 after first medication intake
Self-Reported Total Sleep Time
Time frame: Change from baseline to day 18 after first medication intake
Self-reported Sleep Onset Latency (min)
Time frame: Change from baseline to day 18 after first medication intake
Self-reported Sleep Onset Latency (evaluation)
Time frame: Change from baseline to day 18 after first medication intake
Results and safety
The study was stopped early (reason given: Recruiting problems because of the time expenditure required for participating and the strict criteria of inclusion and exclusion). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Winfried Rief, Prof. Dr. principal investigator
Clinical Psychology and Psychotherapy, Department of Psychology, Philipps University Marburg
Bettina K Doering, Dr. principal investigator
Clinical Psychology and Psychotherapy, Department of Psychology, Philipps University Marburg
Carmen Schade-Brittinger study chair
Koordinierungszentrum für Klinische Studien Marburg, Philipps University Marburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Amitriptyline and Zolpidem in people with Insomnia, run by Philipps University Marburg at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Recruiting problems because of the time expenditure required for participating and the strict criteria of inclusion and exclusion). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Total Sleep Time (time frame: Change from baseline to day 10 after first medication intake). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2018.