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Alternative Dosing Regimens in the Pharmacotherapy of Insomnia (ALPHASOM)

Primary Purpose

Insomnia

Status
Terminated
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Amitriptyline
Zolpidem
Amitriptyline
Placebo
Sponsored by
Philipps University Marburg Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Insomnia focused on measuring sleep architecture, conditioning of pharmacological responses, insomnia

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. age between 18 years to 69 years
  2. fluent in German language
  3. provide written informed consent
  4. ability to understand the explanations and instructions given by the study physician and the investigator

Exclusion Criteria:

  1. Sleep disorders caused by medical factors (e.g. sleep apnea, restless legs syndrome, narcolepsy, substance-induced insomnia)

  2. 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
    • 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
  3. Allergies to ingredients of placebo or novel-tasting drink (CS)
  4. currently pregnant (verified by urine pregnancy test) or lactating
  5. patients scoring ≥12 on the Epworth Sleepiness Scale
  6. patients scoring below 8 or above 21 on the Insomnia Severity Index
  7. 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)
  8. nicotine consumption > 10 cigarettes/day
  9. unwillingness to refrain from alcohol consumption throughout the study
  10. 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)
  11. change in concomitant medication regime during the last 2 weeks prior to visit 1 or after randomization
  12. intake of psychotropic medication during the last 3 months
  13. participation in any other clinical trial 3 months prior to visit 1
  14. women of childbearing age not using 2 highly effective contraceptive methods
  15. employee of the Sponsor or the principal investigator

Sites / Locations

  • Clinical Psychology and Psychotherapy, Department of Psychology, Philipps University Marburg

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Active Comparator

Active Comparator

Active Comparator

Arm Label

Amitriptyline flexible dosing

Zolpidem flexible dosing

Amitriptyline fixed dosing

Zolpidem fixed dosing

Amitriptyline continuous dosing

Arm Description

50 mg capsule amitriptyline before going to bed on 8 out of 17 nights/placebo

5 mg capsule zolpidem before going to bed on 8 out of 17 nights/placebo

50 mg capsule amitriptyline before going to bed on 8 out of 17 nights

5 mg capsule zolpidem before going to bed on 8 out of 17 nights

50 mg capsule amitriptyline before going to bed on 13 out of 17 nights

Outcomes

Primary Outcome Measures

Objective Total Sleep Time
assessed by polysomnography
Objective Sleep Onset Latency
assessed by polysomnography
Self-reported Total Sleep Time
assessed by sleep diary
Self-Reported Sleep Onset Latency
assessed by sleep diary

Secondary Outcome Measures

Percentage of REM sleep
assessed by polysomnography
REM onset latency
assessed by polysomnography
Objective Sleep Efficiency
assessed by actigraphy
Objective Total Sleep Time
assessed by actigraphy
Self-Reported Total Sleep Time
assessed by sleep diary
Self-reported Sleep Onset Latency (min)
assessed by sleep diary
Self-reported Sleep Onset Latency (evaluation)
assessed by sleep diary

Full Information

First Posted
April 24, 2014
Last Updated
March 7, 2018
Sponsor
Philipps University Marburg Medical Center
Collaborators
Johannes Gutenberg University Mainz, Philipps University Marburg Coordination Centre for Clinical Trials
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1. Study Identification

Unique Protocol Identification Number
NCT02139098
Brief Title
Alternative Dosing Regimens in the Pharmacotherapy of Insomnia
Acronym
ALPHASOM
Official Title
Phase III Study on Alternative Dosing Regimens in the Pharmacotherapy of Mild to Moderate Insomnia
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Terminated
Why Stopped
Recruiting problems because of the time expenditure required for participating and the strict criteria of inclusion and exclusion
Study Start Date
May 2014 (undefined)
Primary Completion Date
November 2017 (Actual)
Study Completion Date
November 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Philipps University Marburg Medical Center
Collaborators
Johannes Gutenberg University Mainz, Philipps University Marburg Coordination Centre for Clinical Trials

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Insomnia
Keywords
sleep architecture, conditioning of pharmacological responses, insomnia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Amitriptyline flexible dosing
Arm Type
Experimental
Arm Description
50 mg capsule amitriptyline before going to bed on 8 out of 17 nights/placebo
Arm Title
Zolpidem flexible dosing
Arm Type
Experimental
Arm Description
5 mg capsule zolpidem before going to bed on 8 out of 17 nights/placebo
Arm Title
Amitriptyline fixed dosing
Arm Type
Active Comparator
Arm Description
50 mg capsule amitriptyline before going to bed on 8 out of 17 nights
Arm Title
Zolpidem fixed dosing
Arm Type
Active Comparator
Arm Description
5 mg capsule zolpidem before going to bed on 8 out of 17 nights
Arm Title
Amitriptyline continuous dosing
Arm Type
Active Comparator
Arm Description
50 mg capsule amitriptyline before going to bed on 13 out of 17 nights
Intervention Type
Drug
Intervention Name(s)
Amitriptyline
Intervention Description
50 mg capsule amitriptyline before going to bed on 8 out of 17 nights
Intervention Type
Drug
Intervention Name(s)
Zolpidem
Intervention Description
5 mg capsule zolpidem before going to bed on 8 out of 17 nights
Intervention Type
Drug
Intervention Name(s)
Amitriptyline
Intervention Description
50 mg capsule amitriptyline before going to bed on 13 out of 17 nights
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Objective Total Sleep Time
Description
assessed by polysomnography
Time Frame
Change from baseline to day 10 after first medication intake
Title
Objective Sleep Onset Latency
Description
assessed by polysomnography
Time Frame
Change from baseline to day 10 after first medication intake
Title
Self-reported Total Sleep Time
Description
assessed by sleep diary
Time Frame
Change from baseline to day 10 after first medication intake
Title
Self-Reported Sleep Onset Latency
Description
assessed by sleep diary
Time Frame
Change from baseline to day 10 after first medication intake
Secondary Outcome Measure Information:
Title
Percentage of REM sleep
Description
assessed by polysomnography
Time Frame
Change from baseline to day 10 after first medication intake
Title
REM onset latency
Description
assessed by polysomnography
Time Frame
Change from baseline to day 10 after first medication intake
Title
Objective Sleep Efficiency
Description
assessed by actigraphy
Time Frame
Change from baseline to day 17 after first medication intake
Title
Objective Total Sleep Time
Description
assessed by actigraphy
Time Frame
Change from baseline to day 17 after first medication intake
Title
Self-Reported Total Sleep Time
Description
assessed by sleep diary
Time Frame
Change from baseline to day 18 after first medication intake
Title
Self-reported Sleep Onset Latency (min)
Description
assessed by sleep diary
Time Frame
Change from baseline to day 18 after first medication intake
Title
Self-reported Sleep Onset Latency (evaluation)
Description
assessed by sleep diary
Time Frame
Change from baseline to day 18 after first medication intake

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Winfried Rief, Prof. Dr.
Organizational Affiliation
Clinical Psychology and Psychotherapy, Department of Psychology, Philipps University Marburg
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bettina K Doering, Dr.
Organizational Affiliation
Clinical Psychology and Psychotherapy, Department of Psychology, Philipps University Marburg
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Carmen Schade-Brittinger
Organizational Affiliation
Koordinierungszentrum für Klinische Studien Marburg, Philipps University Marburg
Official's Role
Study Chair
Facility Information:
Facility Name
Clinical Psychology and Psychotherapy, Department of Psychology, Philipps University Marburg
City
Marburg
State/Province
Hessen
ZIP/Postal Code
35032
Country
Germany

12. IPD Sharing Statement

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Alternative Dosing Regimens in the Pharmacotherapy of Insomnia

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