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Partial Reinforcement II: Three Approaches to Maintenance Therapy for Chronic Insomnia (R01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03774810
Recruitment Status : Recruiting
First Posted : December 13, 2018
Last Update Posted : July 7, 2020
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Information provided by (Responsible Party):
University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE December 10, 2018
First Posted Date  ICMJE December 13, 2018
Last Update Posted Date July 7, 2020
Actual Study Start Date  ICMJE April 15, 2019
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 11, 2018)
Insomnia Relapse [ Time Frame: 1 year ]
Tracking Relapse via assessing daily sleep diary responses.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2018)
Sleep Continuity [ Time Frame: 1 year ]
Assess sleep continuity by assessing daily sleep diary responses.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Partial Reinforcement II: Three Approaches to Maintenance Therapy for Chronic Insomnia
Official Title  ICMJE Three Approaches to Maintenance Therapy for Chronic Insomnia in Older Adults
Brief Summary

The study is a three phase sequential study of the medical treatment of insomnia with zolpidem. All participating subjects will receive one month of standard nightly treatment. If the subject has a positive treatment response they continue in the study and are randomized to one of four conditions: intermittent dosing (3-5 pills week, full dose), or one of three variable dose conditions (nightly pill use where any given pill is a variable dose). Standard treatment will last for 4 weeks. The experimental phase will extend over two periods. The first period will last for 12 weeks. The second period will last for 36 weeks. Both periods include:

• Taking a pill 30 minutes prior to bedtime.

In one case, this will involve taking 3-5 pills per week. In the remaining condition pills will be taken on each and every night. Depending on the specific group that the subject is assigned to, they will either receive 10mg or 5mg of zolpidem (variable by age and sex) or a variable dose of zolpidem on a nightly basis (range from 0 mg to 10 mg per night).

  • Completing a sleep diary each day;
  • Completing 6 to 7 questionnaires each week;
  • A monthly visit to Penn to return your medication foil packs and to receive a new foil pack with the next month of medication.

During Phases 3&4, the subject will be asked to undergo quarter annual physicals so that we can optimally track their health and wellbeing. The physicals will involve standard vitals measures (e.g., temperature, blood pressure, height and weight, etc.) and, based on the judgement of the research clinician, may involve an EKG and blood and urine chemistries.

If the subject does not experience a treatment response or (following a treatment response) experiences a relapse of insomnia, they will not continue in the study but will be given the opportunity to be treated with Cognitive Behavioral Therapy for Insomnia (CBT-I) at no cost. Assessments of the subjects clinical status will be based on your daily sleep diaries and weekly questionnaires.

Detailed Description

Phase-1: Initial Evaluation.

This evaluation occurs at the offices of the Behavioral Sleep Medicine Program (Suite 670, 3535 Market Street Philadelphia, PA 19104) and lasts about 1 to 2 hours. Procedures include:

  • Completing forms asking questions about your sleep, mood, alcohol use, medical history, your current medications, and background questions about your age, race, and education.
  • The provision of your consent to contact your primary care provider to gain their assent (agreement) that you may participate in the trial safely.

The information obtained during the initial assessment will be used to see if you are eligible to participate in this study. If you are determined ineligible, you will not be able to continue in the study but will be provided with a referral if appropriate.

NOTE: This study will be using an Internet Data Portal (IDP) system to collect most questionnaire data. The IDP is a Research Electronic Data Capture and is a secure web application. It is a password protected site located on Penn's servers in which the data will live in a database online where only qualified research personnel can access it. During the initial evaluation you will be introduced to this system and provided with a username and password. The study staff will assist you in filling out the questionnaires using this IDP system.

Phase-2: Baseline Period.

This phase lasts 14 days. Your participation includes:

  • Completing daily sleep diaries at home. The online diary form requires about 5 minutes each day to complete.
  • Completing 6 to 7 forms asking questions about your medical symptoms, and sleep each week of the baseline period. These online questionnaires require about 15 minutes to complete.
  • Abstaining from the use of any medication or over the counter product that is used expressly for the purpose of helping you fall or stay asleep (e.g. trazadone/Desyrel, melatonin, Nyquil, Tylenol PM, Benadryl, etc.). If you choose to discontinue your current sleep medication to participate in our study, please do this in consultation with the clinician that prescribed your sleep medication. Please note that discontinuation of your current sleep medication will make it necessary to extend the baseline component of our study by at least two weeks. Should the sleep diaries indicate that your insomnia is not of the type, severity, or frequency required for the study, you will not be able to continue in the study but will be provided with a referral. This referral will be for the Penn Sleep Disorder Center. If you or study personnel deem your two weeks to be unusual, you may be offered the chance to repeat the baseline period.

Phase-3: Sleep Lab Study (polysomnography) or Home Sleep Apnea Test (HSAT). You will undergo a polysomnography study or an HSAT to determine if you are eligible to continue in the study. During the pandemic all sleep tests will be administered at home. After the pandemic, the study investigators will decide which type of study you will receive. Both sleep assessments will last for 1 night.

The HSAT equipment will be shipped to your house. A member of the study team will contact you to go over proper use instructions. On the night of the test, you can go to bed at your regular bedtime. Prior to bedtime, you will attach the sensor(s) as instructed and start the test. Upon waking up, you will stop the test and remove the sensor(s). On the day immediately following the sleep test, you will ship the device back in the prepaid shipping envelope Procedures for the polysomnography study are: you will be asked to arrive at the sleep lab located at the Hospital of the University of Pennsylvania (HUP) at the cross streets of 34th and Spruce by 7 P.M. for a polysomnographic study (PSG). Upon arrival, to ensure for accurate laboratory measurements, urine toxicology screens may be performed to rule out illegal substance use. These data are acquired to explain abnormal findings on the PSG. Following the sleep study, it will be determined whether a repeat study is necessary based on the findings both from the clinical chemistries and the polysomnography. If a repeat study is necessary, one of the project investigators will discuss the issue of substance use with you to: (1) determine if the clinical chemistries' finding was an error (for example poppy seeds led to a positive screen) or (2) gain your willingness to refrain from substance use for the second PSG and for the remainder of the study. If you screen positive a second time, your participation will be discontinued.

The specific procedure for a PSG requires that you have a set of sensors placed on your face, scalp, and body by a technician. All the sensors are attached with surgical tape, paste and glue. The sensors on your face are attached on your left and right temple, cheek bone and under your nose. The sensors on the temple and cheek bone measure eye movements associated with falling asleep and dreaming. The sensors under your nose measure airflow through your mouth and nose. The sensors on your scalp measure brain waves during sleep. The sensors on the body are placed above the collar bones and over the calf muscles. The sensors over the collar bones measure heart muscle activity. The sensors over the calf muscles measure muscle activity from the legs. In addition, a strap will be placed around your chest and abdomen to measure respiration.

After you have been connected to the equipment, you are expected to stay in bed until final wake time the next morning, except for bathroom breaks. You will be visually monitored by the lab technicians by remote video. In the morning, you will be awakened by the technician (if needed), be unhooked from the equipment, and then allowed to shower, dress, and eat before leaving. You will be free to go about your normal schedule for the rest of the day.

If the in-lab PSG sleep or HSAT study finds evidence of a sleep disorder other than insomnia, such as sleep apnea, you will not be able to continue in the study but will be provided with a referral.

Phase-4: Standard Treatment. All participating subjects will receive one month of standard nightly treatment. If you have a positive treatment response you will remain in the study and be randomized to one of the following treatment conditions: nightly dosing, intermittent dosing (1-3 pills week, full dose), or one of two variable dose conditions (nightly pill use where any given pill is a variable dose). The assignment of condition will be accomplished by a process that is the same as the flip of a coin and neither you nor the study personnel will know which condition you have been assigned to (this is referred to as a "double blind" study). You will have an equal chance of being randomized to each of the 4 study arms. In the case of an emergency, the blind will be broken and the study doctor and clinicians associated with your care will be informed of which dosing condition you were assigned to.

Standard treatment will last for 4 weeks. The experimental phase will extend over two periods. The first period will last for 12 weeks. The second period will last for 36 weeks.

Both periods include:

  • Taking a pill 30 minutes prior to bedtime. In one case, this will involve taking 1-3 pills per week. In the remaining conditions, pills will be taken on each and every night. Depending on the specific group you are assigned to, you will either receive 10mg or 5mg of zolpidem (variable by age and sex) or a variable dose of zolpidem on a nightly basis (range from 0 mg to 10 mg per night). Please note that the effect of zolpidem may be slowed if taken with or immediately after a meal.
  • Completing a sleep diary each day;
  • Completing 6 to 7 questionnaires each week;
  • A monthly visit to Penn to return your medication foil packs and to receive a new foil pack with the next month of medication.

If you do not experience a treatment response or (following a treatment response) you experience a relapse of insomnia, you will not be able to continue in the study but will be given the opportunity to be treated with Cognitive Behavioral Therapy for Insomnia (CBT-I) at no cost. Assessments of your clinical status (how your insomnia is responding to treatment) will be based on your daily sleep diaries and weekly questionnaires.

During Phase-4, you will be asked to undergo quarter annual physicals so that we can optimally track your health and wellbeing. The physicals will involve standard vital measures (e.g., temperature, blood pressure, height and weight, etc.) and, based on the judgement of the research clinician, may involve an EKG and/or blood and urine chemistries.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double Blinded
Primary Purpose: Treatment
Condition  ICMJE
  • Insomnia
  • Insomnia Chronic
Intervention  ICMJE Drug: Zolpidem tartrate
Zolpidem Tartrate, 5mg for men older than 60 and women of all ages. 10 mg for men younger than 60.
Other Names:
  • zolpidem
  • ambien
Study Arms  ICMJE
  • Experimental: Continuous
    Nightly active dose (QHS). The intervention is zolpidem tartrate 5 mg or 10 mg.
    Intervention: Drug: Zolpidem tartrate
  • Experimental: Partial Reinforcement 1
    1 active dose per week with 6 placebos interspersed between the active dose. The intervention is zolpidem tartrate 5 mg or 10 mg.
    Intervention: Drug: Zolpidem tartrate
  • Experimental: Partial Reinforcement 3
    3 active doses per week with 4 placebos interspersed between the active doses. The intervention is zolpidem tartrate 5 mg or 10 mg.
    Intervention: Drug: Zolpidem tartrate
  • Experimental: Low Frequency Intermittent Dosing
    1 to 3 active doses per week PRN. The intervention is zolpidem tartrate 5 mg or 10 mg.
    Intervention: Drug: Zolpidem tartrate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 11, 2018)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2022
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with chronic insomnia will meet DSM-5 criteria for Insomnia Disorder, ICSD-3, and RDC criteria for Psychophysiologic Insomnia. In addition, all subjects will have a sleep initiation and/or a sleep maintenance complaint (> 30 min. to fall asleep and/or > 30 min. of wakefulness during the night) with a problem frequency > 3 nights/wk and problem duration > 3 mo. This profile must be evident at both intake (based on retrospective reports) and as an average profile from the two weeks of baseline diaries (prospective sampling).

Exclusion Criteria:

  • currently in treatment for insomnia, unstable medical or psychiatric illness, a history of treatment failure with zolpidem, discontinuation of zolpidem owing to side effects, and/or current experience, or history, of parasomnias (within the last 5 years).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mark Seewald, BS 2157464378 mark.seewald@upenn.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03774810
Other Study ID Numbers  ICMJE 831801
R01AG054521-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Pennsylvania
Study Sponsor  ICMJE University of Pennsylvania
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • National Institute on Aging (NIA)
Investigators  ICMJE
Principal Investigator: Michael L Perlis, PhD University of Pennsylvania
PRS Account University of Pennsylvania
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP