Alternative Dosing Regimens in the Pharmacotherapy of Insomnia (ALPHASOM)

March 7, 2018 updated by: Winfried Rief, Philipps University Marburg Medical Center

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
23

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Hessen
      • Marburg, Hessen, Germany, 35032
        • Clinical Psychology and Psychotherapy, Department of Psychology, Philipps University Marburg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 69 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Amitriptyline flexible dosing
50 mg capsule amitriptyline before going to bed on 8 out of 17 nights/placebo
Drug: Placebo
Placebo
Drug: Amitriptyline
50 mg capsule amitriptyline before going to bed on 8 out of 17 nights
Drug: Amitriptyline
50 mg capsule amitriptyline before going to bed on 13 out of 17 nights
Experimental: Zolpidem flexible dosing
5 mg capsule zolpidem before going to bed on 8 out of 17 nights/placebo
Drug: Placebo
Placebo
Drug: Zolpidem
5 mg capsule zolpidem before going to bed on 8 out of 17 nights
Active Comparator: Amitriptyline fixed dosing
50 mg capsule amitriptyline before going to bed on 8 out of 17 nights
Drug: Amitriptyline
50 mg capsule amitriptyline before going to bed on 8 out of 17 nights
Drug: Amitriptyline
50 mg capsule amitriptyline before going to bed on 13 out of 17 nights
Active Comparator: Zolpidem fixed dosing
5 mg capsule zolpidem before going to bed on 8 out of 17 nights
Drug: Zolpidem
5 mg capsule zolpidem before going to bed on 8 out of 17 nights
Active Comparator: Amitriptyline continuous dosing
50 mg capsule amitriptyline before going to bed on 13 out of 17 nights
Drug: Amitriptyline
50 mg capsule amitriptyline before going to bed on 8 out of 17 nights
Drug: Amitriptyline
50 mg capsule amitriptyline before going to bed on 13 out of 17 nights

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Objective Total Sleep Time
Time Frame: Change from baseline to day 10 after first medication intake
assessed by polysomnography
Change from baseline to day 10 after first medication intake
Objective Sleep Onset Latency
Time Frame: Change from baseline to day 10 after first medication intake
assessed by polysomnography
Change from baseline to day 10 after first medication intake
Self-reported Total Sleep Time
Time Frame: Change from baseline to day 10 after first medication intake
assessed by sleep diary
Change from baseline to day 10 after first medication intake
Self-Reported Sleep Onset Latency
Time Frame: Change from baseline to day 10 after first medication intake
assessed by sleep diary
Change from baseline to day 10 after first medication intake

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of REM sleep
Time Frame: Change from baseline to day 10 after first medication intake
assessed by polysomnography
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
assessed by polysomnography
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
assessed by actigraphy
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
assessed by actigraphy
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
assessed by sleep diary
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
assessed by sleep diary
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
assessed by sleep diary
Change from baseline to day 18 after first medication intake

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Philipps University Marburg Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Johannes Gutenberg University Mainz
Philipps University Marburg Coordination Centre for Clinical Trials

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Winfried Rief, Prof. Dr., Clinical Psychology and Psychotherapy, Department of Psychology, Philipps University Marburg
  • Principal Investigator: Bettina K Doering, Dr., Clinical Psychology and Psychotherapy, Department of Psychology, Philipps University Marburg
  • Study Chair: Carmen Schade-Brittinger, Koordinierungszentrum für Klinische Studien Marburg, Philipps University Marburg

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 24, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 13, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 15, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 9, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 7, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FOR1328-SP8
  • 2013-003229-27 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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