Primary InsomniaADERNCT00662155
The Role of Partial Reinforcement in the Long Term Management of Insomnia
A study testing Zolpidem in people with Primary Insomnia, run by University of Pennsylvania at 1 site in United States.
Trial summary
The lack of scientific attention devoted to the placebo effect as a phenomenon in its own right probably reflects the paucity of theoretical positions within which to organize the existing data and design new research. Read more about this study
- Who is it for?
- Ages 21 to 55 years
- Conditions the study is for
- Primary Insomnia
- What is being tested?
- Zolpidem
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 129 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2006to Jun 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients with insomnia will meet RDC criteria for psychophysiologic insomnia(99). These criteria are provided in Appendix 2. In addition, the complaint of disturbed sleep will have one or more of the following characteristics:
- > 30 minutes to fall asleep (Initial Insomnia)
- 2 awakenings per night of >15 minutes duration and/or wake after sleep onset time of > 30 minutes (Middle Insomnia)
- An awakening of > 30 minutes prior to the desired "wake up" time (Late Insomnia)
- Any two of the above complaints (Mixed Insomnia)
- Additionally, total sleep time will not exceed 6 hours (unless the sleep efficiency quotient is < 80%) and the problem frequency must be equal to or greater than 4 nights/ week (severe insomnia) with a problem duration > 6 months (chronic insomnia). This profile must be evident at both intake (based on retrospective reports) and as an average profile from the two weeks of baseline diaries (based on prospective sampling).
Who cannot join
- Unstable medical or psychiatric illness Assessed with the Mini International Neuropsychiatric Interview (MINI) and the The Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) To assure that the insomnia is not secondary to these factors
- Symptoms suggestive of sleep disorders other than insomnia Assessed with the SDS-CL To assure that the insomnia is not secondary to these factors
- Polysomnographic data indicating sleep disorders other than insomnia Assessed with PSG in collaboration with our sleep medicine consultants To assure that the insomnia is not secondary to these factors
- History of head injury with a sustained loss of consciousness Assessed by self report during the Intake Interview To help assure that the EEG measures are unconfounded by brain damage
- Evidence of active illicit substance use or fitting criteria for alcohol abuse or dependence Assessed with a structured psychiatric interview schedule (the MINI) , written versions of clinical interview queries regarding alcohol use, abuse and dependence (the AUDIT and CAGE), the toxicology screen which is part of the clinical chemistries obtained during the screening physical. To assure that the insomnia is not secondary to these factors and to assure that substance use/abuse does not confound treatment.
- Use of CNS active medications, antidepressants, and hypnotics other than zolpidem Assessed by self report and from the toxicology screen which is part of the clinical chemistries obtained during the screening physical. To help assure that the clinical effects observed in this study are due to the study medication and schedule of reinforcement.
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- Inadequate language comprehension Informally, assessed by the Clinical Research Coordinator during Intake Interview To assure the quality of self report data as all the measures are in English.
- Pregnancy Assessed by self report and from the clinical chemistries data obtained during the screening physical. Excluded so as to 1) prevent the fetus from exposure to the study medication (although it should be noted that the medication is considered FDA pregnancy category B) and 2) control for the biopsychosocial changes that occur with pregnancy and may alter the response to the study medication and schedule of reinforcement.
- No first-degree relatives with bipolar disorder or schizophrenia Assessed by self report and a structured psychiatric interview schedule (the SADs). Excluded to reduce risk for first onset during the study
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
The lack of scientific attention devoted to the placebo effect as a phenomenon in its own right probably reflects the paucity of theoretical positions within which to organize the existing data and design new research. The proposed investigation 1) is an attempt to advance from a descriptive to an experimental analysis of the placebo effect, taking into account classical conditioning effects, and 2) examines the clinical implications of partial reinforcement as it is applied to the treatment of insomnia. Subjects with primary insomnia will be treated with zolpidem for a period of one month and then randomized to one of four groups for a period of 12 weeks: one receiving full dose zolpidem on a nightly basis (continuous reinforcement), one receiving full dose zolpidem on 14 of 28 nights where placebo is provided on non-drug nights (partial reinforcement), one receiving full dose zolpidem on 14 of 28 nights where no pills are imbibed on non-drug nights (intermittent dosing), and one receiving 5 mg dose zolpidem on a nightly basis (continuous reinforcement with half the standard dose). Following treatment, subjects will be entered into an extinction protocol during which they will 1) continue on the schedule assigned during the experimental period, 2) receive only placebo, or 3) receive neither drug nor placebo. Sleep and daily functioning will be monitored on a daily basis via sleep diaries for the duration of the study. It is hypothesized that, holding cumulative dose constant, a partial schedule of reinforcement will enable patients to better maintain their clinical gains as compared to subjects that receive either continuous reinforcement with half the standard dose or half the frequency of use.
Relevance: The proposed research is not an attempt to offer a behavioral alternative to drug treatment; it is an attempt to acknowledge and capitalize on a behavioral dimension in the design of drug treatment protocols. The value of the proposed research resides in its capacity to provide for the long term treatment of insomnia in a manner that increases the durability of pharmacotherapy while reducing the overall amount of medication required. If proven effective in the current application, this new approach to pharmacotherapy and placebo effects is likely to stimulate new interdisciplinary research for the treatment of a variety of chronic diseases.
- Conditions
- Primary Insomnia
- Being tested
- Zolpidem, Placebos
- Keywords
- Primary Insomnia, Cognitive Behavioral Therapy, Insomnia, Sleep, Zolpidem, Ambien, CBT, CBT-I
- 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.
ZolpidemDrug
Also called Ambien
sedative-hypnotic
PlacebosDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Continuous 1 (QHS-10) | Experimental | continued nightly use with 10mg zolpidem Receives: Drug: Zolpidem |
| Partial Reinforcement (PRS-10) | Experimental | partial reinforcement with 10mg zolpidem (PRS-10 [nightly pill use with 50% active meds and 50% placebos]) Receives: Drug: Zolpidem; Drug: Placebos |
| Intermittent (IDS-10) | Experimental | intermittent dosing with 10mg zolpidem Receives: Drug: Zolpidem |
| Continuous 2 (QHS-5) | Experimental | continued nightly use with 5mg zolpidem Receives: Drug: Zolpidem |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Average Sleep Continuity Profile
The standard measure for clinical trials research in insomnia is the sleep diary. This prospective self-report measurement tool provides an assessment of sleep continuity as a function of treatment.
Measured: 12-week average during Phase 3
Overall Average Sleep Efficiency (%)
The standard measure for clinical trials research in insomnia is the sleep diary. This prospective self-report measurement tool provides an assessment of sleep efficiency (total sleep time/time in bed x 100) as a function of treatment.
Measured: 12-week average during Phase 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2008 (estimated)
- Study startJul 2006
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary InsomniaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 129 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Center for Complementary and Integrative Health (NCCIH)
- Responsible party
- Sponsor
- Investigators
- Michael Perlis, Ph.D., Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00662155
- Sponsor's protocol ID
- RSRB # 14533
- Other IDs
- 1R01AT003332-01A1
- Acronym
- ADER
- Status last verified
- Jul 2017
- First submitted
- 16 Apr 2008
- Last updated
- 7 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Partial Reinforcement in the Long Term Management of Insomnia
- ClinicalTrials.gov ID
- NCT00662155
- Acronym / sponsor ID
- ADER / RSRB # 14533
- Conditions
- Primary Insomnia
- Keywords
- Primary Insomnia, Cognitive Behavioral Therapy, Insomnia, Sleep, Zolpidem, Ambien, CBT, CBT-I
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 129 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Center for Complementary and Integrative Health (NCCIH)
- Study start
- Jul 2006
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 21 Apr 2008 (estimated)
- Results
- Posted 7 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The lack of scientific attention devoted to the placebo effect as a phenomenon in its own right probably reflects the paucity of theoretical positions within which to organize the existing data and design new research. The proposed investigation 1) is an attempt to advance from a descriptive to an experimental analysis of the placebo effect, taking into account classical conditioning effects, and 2) examines the clinical implications of partial reinforcement as it is applied to the treatment of insomnia. Subjects with primary insomnia will be treated with zolpidem for a period of one month and then randomized to one of four groups for a period of 12 weeks: one receiving full dose zolpidem on a nightly basis (continuous reinforcement), one receiving full dose zolpidem on 14 of 28 nights where placebo is provided on non-drug nights (partial reinforcement), one receiving full dose zolpidem on 14 of 28 nights where no pills are imbibed on non-drug nights (intermittent dosing), and one receiving 5 mg dose zolpidem on a nightly basis (continuous reinforcement with half the standard dose). Following treatment, subjects will be entered into an extinction protocol during which they will 1) continue on the schedule assigned during the experimental period, 2) receive only placebo, or 3) receive neither drug nor placebo. Sleep and daily functioning will be monitored on a daily basis via sleep diaries for the duration of the study. It is hypothesized that, holding cumulative dose constant, a partial schedule of reinforcement will enable patients to better maintain their clinical gains as compared to subjects that receive either continuous reinforcement with half the standard dose or half the frequency of use.
Relevance: The proposed research is not an attempt to offer a behavioral alternative to drug treatment; it is an attempt to acknowledge and capitalize on a behavioral dimension in the design of drug treatment protocols. The value of the proposed research resides in its capacity to provide for the long term treatment of insomnia in a manner that increases the durability of pharmacotherapy while reducing the overall amount of medication required. If proven effective in the current application, this new approach to pharmacotherapy and placebo effects is likely to stimulate new interdisciplinary research for the treatment of a variety of chronic diseases.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Continuous 1 (QHS-10) | Experimental | Drug: Zolpidemcontinued nightly use with 10mg zolpidem |
| Partial Reinforcement (PRS-10) | Experimental | Drug: Zolpidem, Drug: Placebospartial reinforcement with 10mg zolpidem (PRS-10 [nightly pill use with 50% active meds and 50% placebos]) |
| Intermittent (IDS-10) | Experimental | Drug: Zolpidemintermittent dosing with 10mg zolpidem |
| Continuous 2 (QHS-5) | Experimental | Drug: Zolpidemcontinued nightly use with 5mg zolpidem |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Patients with insomnia will meet RDC criteria for psychophysiologic insomnia(99). These criteria are provided in Appendix 2. In addition, the complaint of disturbed sleep will have one or more of the following characteristics:
- Additionally, total sleep time will not exceed 6 hours (unless the sleep efficiency quotient is < 80%) and the problem frequency must be equal to or greater than 4 nights/ week (severe insomnia) with a problem duration > 6 months (chronic insomnia). This profile must be evident at both intake (based on retrospective reports) and as an average profile from the two weeks of baseline diaries (based on prospective sampling).
Key exclusion criteria (9 listed)
- Unstable medical or psychiatric illness Assessed with the Mini International Neuropsychiatric Interview (MINI) and the The Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) To assure that the insomnia is not secondary to these factors
- Symptoms suggestive of sleep disorders other than insomnia Assessed with the SDS-CL To assure that the insomnia is not secondary to these factors
- Polysomnographic data indicating sleep disorders other than insomnia Assessed with PSG in collaboration with our sleep medicine consultants To assure that the insomnia is not secondary to these factors
- History of head injury with a sustained loss of consciousness Assessed by self report during the Intake Interview To help assure that the EEG measures are unconfounded by brain damage
- Evidence of active illicit substance use or fitting criteria for alcohol abuse or dependence Assessed with a structured psychiatric interview schedule (the MINI) , written versions of clinical interview queries regarding alcohol use, abuse and dependence (the AUDIT and CAGE), the toxicology screen which is part of the clinical chemistries obtained during the screening physical. To assure that the insomnia is not secondary to these factors and to assure that substance use/abuse does not confound treatment.
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 |
|---|---|---|
| ZolpidemAlso: Ambiensedative-hypnotic | Drug | Continuous 1 (QHS-10), Continuous 2 (QHS-5), Intermittent (IDS-10), Partial Reinforcement (PRS-10) |
| PlacebosPlacebo | Drug | Partial Reinforcement (PRS-10) |
Primary outcome
Overall Average Sleep Continuity Profile
Time frame: 12-week average during Phase 3
The standard measure for clinical trials research in insomnia is the sleep diary. This prospective self-report measurement tool provides an assessment of sleep continuity as a function of treatment.
Overall Average Sleep Efficiency (%)
Time frame: 12-week average during Phase 3
The standard measure for clinical trials research in insomnia is the sleep diary. This prospective self-report measurement tool provides an assessment of sleep efficiency (total sleep time/time in bed x 100) as a function of treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- (Click here to learn about our available studies)Link provided by the sponsor.
- (Click here to learn more about our sleep research laboratory)Link provided by the sponsor.
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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.
Michael Perlis, Ph.D. principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Zolpidem in people with Primary Insomnia, run by University of Pennsylvania at 1 site in United States.
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 6 inclusion and 9 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: finished, as of the sponsor's last update on 7 Aug 2017. 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 United States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Average Sleep Continuity Profile (time frame: 12-week average during Phase 3). The study lists 2 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 7 Aug 2017.