The Treatment of Insomnia Comorbid With Sleep Disordered Breathing Using Armodafinil and/or Cognitive Behavioral Therapy for Insomnia

Insomnia Clinical Trial

Official title:

The Treatment of Insomnia Comorbid With Sleep Disordered Breathing Using Armodafinil and/or Cognitive Behavioral Therapy for Insomnia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02552303
• Other study ID #: 817800
• Status: Active, not recruiting
• Phase: N/A
• First received: September 9, 2015
• Last updated: June 3, 2016
• Start date: April 2014
• Est. completion date: January 2017

Study information

• Verified date: June 2016
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the effects of Armodafinil, CBT-I, or the combination of the two on the sleep continuity of persons suffering from sleep disordered breathing and their adherence to CBT-I and Continuous Positive Airway Pressure (CPAP). Adults diagnosed with obstructive sleep apnea and who meet additional research and diagnostic criteria for insomnia will be recruited. Participants will submit daily sleep diaries and supplemental questionnaires as measures of study progress.

Description:

Rationale:

Insomnia and sleep disordered breathing are the most common sleep disorders and they tend to be highly comorbid. When they co‐occur, not only is there an increase in cumulative morbidity, but it is likely that these two diseases interact to: promote overall greater illness severity; reduce treatment adherence; and diminish treatment efficacy. The results from the proposed project will provide valuable information on how co‐treatment for these two disorders can promote improved sleep quantity, enhanced sleep quality, better compliance with Positive Airway Pressure (PAP) therapy, and better daytime functioning.

Background:

There is now substantial evidence that Cognitive Behavioral Therapy for Insomnia (CBT‐I) is efficacious for Primary Insomnia (PI), that it is as potent as sedative hypnotic treatment, and better sustained over time. Further, there is now increasing evidence that CBT‐I can be applied to insomnias that are co‐morbid with medical and psychiatric disorders, and with equal efficacy. The evidence for an expanded indication, to date, has been for insomnia comorbid with depression, chronic pain, and cancer. Interestingly, there are very few studies on the efficacy of CBT‐I in insomnia comorbid with other intrinsic sleep disorders, including in patients with Sleep Disordered Breathing (SDB). This is surprising given that insomnia frequently occurs comorbidly with SDB. It is estimated that 40‐60% of patients with SDB also suffer from insomnia. The lack of data regarding the applicability of CBT‐I to insomnia co‐morbid with SDB is likely due to the concern that CBT‐I will be difficult to tolerate in patients with insomnia co‐morbid with SDB given the treatment's tendency to produce acute increases in fatigue, sleepiness, and transient reductions in attention and performance. Accordingly, the investigators of this study propose to conduct a randomized, controlled trial on the effects of Armodafinil alone and in combination with CBT‐I in patients with Insomnia comorbid with SDB.

Note: The choice to evaluate Armodafinil as both a monotherapy and an adjuvant therapy to CBT‐I for insomnia has a firm conceptual basis and is supported by preliminary data from our group. The choice to evaluate Armodafinil in patients with insomnia co‐morbid with SDB is further supported by the existing indication for sleepiness in patients with SDB.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 72
• Est. completion date: January 2017
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 65 Years

Eligibility

Inclusion Criteria:

• eligible subjects must have begun their CPAP treatment within the last 3 months

• current ESS (Sleepiness) Scores between 5-19

• no history of upper airway surgery (e.g. UPPP)

• able to understand written and spoken English

• able to swallow medication

• preferred sleep phase between 9:00 pm and 9:00 am

• willing to discontinue any sleep medications/over-the-counters(OTCs)/Herbals for insomnia for the 11-week study period.

• female participants must not be pregnant or breastfeeding and must agree to use two forms of birth control during the study period, as Armodafinil may interfere with hormonal birth control.

• all participants will be asked to postpone any additional or alternate treatments for their Obstructive Sleep Apnea (OSA) until after the completion of their participation in this research study.

• for other elective procedures, prospective participants are recommended to either postpone the procedure until after completion of their participation in this study, or alternatively to start the study after completion of the elective procedure.

Exclusion Criteria:

• CPAP usage exceeding three months prior to pre-screening

• suicide attempts within the last five years

• unstable medical or psychiatric illness

• cardiac abnormalities, liver, or kidney diseases

• sleep disorders other than insomnia or SDB

• evidence of active illicit substance use or fitting criteria for alcohol abuse or dependence

• use of central nervous system (CNS) active medications, antidepressants and hypnotics prescribed as sleep-aids (these medications are permitted if prescribed for mediation of symptoms other than sleep and the patient has been on a stable dosage for a minimum of one month, with no anticipation of altering their dosage during the study period.)

• inadequate language comprehension

• pregnant or breastfeeding

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Insomnia
• Sleep Apnea

Intervention

Behavioral:
• Cognitive Behavioral Therapy for Insomnia
Cognitive Behavioral Therapy for Insomnia.

Drug:
• Armodafinil
Active medication
• Placebo
Placebo for Nuvigil (armodafinil)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	Teva Pharmaceutical Industries, Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change in Sleep Continuity from baseline to follow-up, as measured by the Insomnia Severity Index (ISI).	This outcome measure is based on changes in sleep continuity, as assessed by the Insomnia Severity Index (ISI), which is administered once at baseline and once at follow-up.; The four different treatment groups will be compared for differences.	ISI is measured once at baseline and once at follow-up (8-10 weeks apart)	No
Secondary	Change in CBT-I attrition rate.	Sleep diary attrition rates are assessed by weekly sleep continuity measures from subject's self-completed sleep diaries. Measures include: sleep latency (SL), wake after sleep onset (WASO), and total sleep time (TST).; Two treatment groups will be compared for differences: 1) CBTI + armodafinil, 2) CBTI + placebo.	average of 8 weeks of active study	No
Secondary	The difference in subject drop-out rates, comparing subjects taking active v. placebo study medication	Drop-out rates will be calculated by the number of protocol weeks the subject completed before withdrawing from the study.; Withdrawal indicates subjects who were either lost-to-follow-up (LTFU), chose to withdraw (self-withdrawn), or were withdrawn by the study's PI (withdrawn by investigator).	up to 8 weeks of active study	No
Secondary	Exploratory Aim: The overall change in Epworth Sleepiness Scale (ESS) scores	Assess how CBT-I and/or Armodafinil affects daytime functioning, as assessed by weekly Epworth Sleepiness Scale (ESS) questionnaires.; All four treatment groups will be evaluated for within-group and between-group differences.	baseline to follow-up (average total of 12 weeks)	No
Secondary	Exploratory Aim: The overall change in Functional Outcomes of Sleep Questionnaire (FOSQ-10) scores	Assess how CBT-I and/or Armodafinil affects daytime functioning, as assessed by the Functional Outcomes of Sleepiness Questionnaire (FOSQ-10).; All four treatment groups will be evaluated for within-group and between-group differences.	baseline to follow-up (average total of 12 weeks)	No
Secondary	Exploratory Aim: The overall change in Brief Fatigue Inventory (BFI) scores	Assess how CBT-I and/or Armodafinil affects daytime functioning, as assessed by the Brief Fatigue Inventory (BFI).; All four treatment groups will be evaluated for within-group and between-group differences.	baseline to follow-up (average total of 12 weeks)	No
Secondary	Exploratory Aim: The overall change in Flinders Fatigue Scale (FFS) scores	Assess how CBT-I and/or Armodafinil affects daytime functioning, as assessed by the Flinders Fatigue Scale (FFS).; All four treatment groups will be evaluated for within-group and between-group differences.	baseline to follow-up (average total of 12 weeks)	No
Secondary	Exploratory Aim: The change in PAP Adherence (hours per night).	Assess how improved sleep continuity from CBT-I affects PAP adherence, as assessed with "smart card" type technology (measures time the PAP unit is used [at pressure] and not just time that the unit is powered on).	8 weeks of active study, 2 weeks of follow-up	No