Alternative Dosing Regimens in the Pharmacotherapy of Insomnia (ALPHASOM)

• ClinicalTrials.gov Identifier: NCT02139098
• Recruitment Status: Terminated
• First Posted: May 15, 2014
• Last Update Posted: March 9, 2018
• Sponsor: Philipps University Marburg Medical Center
• Collaborators: Johannes Gutenberg University Mainz; Philipps University Marburg Coordination Centre for Clinical Trials
• Information provided by (Responsible Party): Winfried Rief, Philipps University Marburg Medical Center

Tracking Information

• First Submitted Date: April 24, 2014
• First Posted Date: May 15, 2014
• Last Update Posted Date: March 9, 2018
• Study Start Date: May 2014
• Actual Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 13, 2014)

• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 13, 2014)

• Percentage of REM sleep [ Time Frame: Change from baseline to day 10 after first medication intake ]
  assessed by polysomnography
• REM onset latency [ Time Frame: Change from baseline to day 10 after first medication intake ]
  assessed by polysomnography
• Objective Sleep Efficiency [ Time Frame: Change from baseline to day 17 after first medication intake ]
  assessed by actigraphy
• Objective Total Sleep Time [ Time Frame: Change from baseline to day 17 after first medication intake ]
  assessed by actigraphy
• Self-Reported Total Sleep Time [ Time Frame: Change from baseline to day 18 after first medication intake ]
  assessed by sleep diary
• Self-reported Sleep Onset Latency (min) [ Time Frame: Change from baseline to day 18 after first medication intake ]
  assessed by sleep diary
• Self-reported Sleep Onset Latency (evaluation) [ Time Frame: Change from baseline to day 18 after first medication intake ]
  assessed by sleep diary

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Alternative Dosing Regimens in the Pharmacotherapy of Insomnia
• Official Title: Phase III Study on Alternative Dosing Regimens in the Pharmacotherapy of Mild to Moderate Insomnia
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Insomnia

Intervention

• Drug: Amitriptyline
  50 mg capsule amitriptyline 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
• Drug: Amitriptyline
  50 mg capsule amitriptyline before going to bed on 13 out of 17 nights
• Drug: Placebo
  Placebo

Study Arms

• Experimental: Amitriptyline flexible dosing
  50 mg capsule amitriptyline before going to bed on 8 out of 17 nights/placebo
  Interventions:

  • Drug: Amitriptyline
  • Drug: Placebo
• Experimental: Zolpidem flexible dosing
  5 mg capsule zolpidem before going to bed on 8 out of 17 nights/placebo
  Interventions:

  • Drug: Zolpidem
  • Drug: Placebo
• Active Comparator: Amitriptyline fixed dosing
  50 mg capsule amitriptyline before going to bed on 8 out of 17 nights
  Intervention: Drug: Amitriptyline
• Active Comparator: Zolpidem fixed dosing
  5 mg capsule zolpidem before going to bed on 8 out of 17 nights
  Intervention: Drug: Zolpidem
• Active Comparator: Amitriptyline continuous dosing
  50 mg capsule amitriptyline before going to bed on 13 out of 17 nights
  Intervention: Drug: Amitriptyline

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 7, 2018): 23
• Original Estimated Enrollment (submitted: May 13, 2014): 150
• Actual Study Completion Date: November 2017
• Actual Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 69 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT02139098
• Other Study ID Numbers: FOR1328-SP8; 2013-003229-27 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Winfried Rief, Philipps University Marburg Medical Center
• Study Sponsor: Philipps University Marburg Medical Center

Collaborators

• Johannes Gutenberg University Mainz
• Philipps University Marburg Coordination Centre for Clinical Trials

Investigators

• 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

• PRS Account: Philipps University Marburg Medical Center
• Verification Date: March 2018