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

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT02552303
• Collaborator: Teva Pharmaceutical Industries, Ltd. (Industry)
• Enrollment: 39
• Arms: 4
• Duration (Months): 15

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Sleep Apnea; Insomnia	Behavioral: Cognitive Behavioral Therapy for Insomnia; Drug: Armodafinil; Drug: Placebo	N/A

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: The Treatment of Insomnia Comorbid With Sleep Disordered Breathing Using Armodafinil and/or Cognitive Behavioral Therapy for Insomnia
• Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: CBT for Insomnia (CBTI) + Armodafinil CBT-I with Armodafinil (active medication)	Behavioral: Cognitive Behavioral Therapy for Insomnia; Cognitive Behavioral Therapy for Insomnia.; Other Names: CBT-I ; Drug: Armodafinil; Active medication; Other Names: NuVigil
Placebo Comparator: CBTI + Placebo Cognitive Behavioral Therapy for Insomnia with Placebo medication	Behavioral: Cognitive Behavioral Therapy for Insomnia; Cognitive Behavioral Therapy for Insomnia.; Other Names: CBT-I ; Drug: Placebo; Placebo for Nuvigil (armodafinil)
Active Comparator: Armodafinil Medication (armodafinil) only, without CBTI.	Drug: Armodafinil; Active medication; Other Names: NuVigil
Placebo Comparator: Placebo Placebo only, without CBTI.	Drug: Placebo; Placebo for Nuvigil (armodafinil)

Outcome Measures

Primary Outcome Measures

1. The Change in Sleep Continuity From Baseline to Follow-up, as Measured by the Insomnia Severity Index (ISI). [ISI is measured once at baseline and once at follow-up (8-10 weeks apart)]

   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 ISI (Morin, 1993) was used to assess perceived sleep difficulties or current insomnia symptom severity (i.e., past two weeks). The ISI is a 7-item, self-report instrument with good reliability and validity, and positively correlated with clinician-rated insomnia diagnoses (Bastien, Vallières, & Morin, 2001). Total scores on the full 7-item scale range from 0 - 28 with higher values representing greater sleep continuity disturbance or insomnia severity. The four different treatment groups will be compared for differences.

Secondary Outcome Measures

1. Number of Subjects Who Dropped Out [up to 8 weeks of active study]

   Drop-out rates will be calculated by the number of protocol weeks the subject completed before withdrawing from the study. Drop out rates for subjects taking active v. placebo study medication were compared. Withdrawal indicates subjects who were either lost-to-follow-up (LTFU), chose to withdraw (self-withdrawn), were withdrawn by the study's PI (withdrawn by the investigator).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• University of Pennsylvania
• Teva Pharmaceutical Industries, Ltd.

Investigators

• Principal Investigator: Michael L Perlis, PhD, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT02552303
• Other Study ID Numbers: 817800
• First Posted: Sep 17, 2015
• Last Update Posted: Jul 31, 2017
• Last Verified: Jun 1, 2017

• Additional relevant MeSH terms: Sleep Apnea Syndromes; Sleep Initiation and Maintenance Disorders; Modafinil

Study Results

Participant Flow

Arm/Group Title	CBT for Insomnia (CBTI) + Armodafinil	CBTI + Placebo	Armodafinil	Placebo
Arm/Group Description	CBT-I with Armodafinil (active medication) Cognitive Behavioral Therapy for Insomnia: Cognitive Behavioral Therapy for Insomnia. Armodafinil: Active medication	Cognitive Behavioral Therapy for Insomnia with Placebo medication Cognitive Behavioral Therapy for Insomnia: Cognitive Behavioral Therapy for Insomnia. Placebo: Placebo for Nuvigil (armodafinil)	Medication (armodafinil) only, without CBTI. Armodafinil: Active medication	Placebo only, without CBTI. Placebo: Placebo for Nuvigil (armodafinil)
Period Title: Allocation
STARTED	10	10	8	11
COMPLETED	7	8	7	10
NOT COMPLETED	3	2	1	1
Period Title: Allocation
STARTED	7	8	7	10
COMPLETED	7	6	6	10
NOT COMPLETED	0	2	1	0

Baseline Characteristics

Arm/Group Title	CBT for Insomnia (CBTI) + Armodafinil	CBTI + Placebo	Armodafinil	Placebo	Total
Arm/Group Description	CBT-I with Armodafinil (active medication) Cognitive Behavioral Therapy for Insomnia: Cognitive Behavioral Therapy for Insomnia. Armodafinil: Active medication	Cognitive Behavioral Therapy for Insomnia with Placebo medication Cognitive Behavioral Therapy for Insomnia: Cognitive Behavioral Therapy for Insomnia. Placebo: Placebo for Nuvigil (armodafinil)	Medication (armodafinil) only, without CBTI. Armodafinil: Active medication	Placebo only, without CBTI. Placebo: Placebo for Nuvigil (armodafinil)	Total of all reporting groups
Overall Participants	10	10	8	11	39
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.2 (9.0)	45.0 (9.8)	48.4 (12.4)	51.9 (7.1)	48.2 (9.5)
Sex: Female, Male (Count of Participants)
Female	7 70%	5 50%	5 62.5%	7 63.6%	24 61.5%
Male	3 30%	5 50%	3 37.5%	4 36.4%	15 38.5%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	8 100%	11 100%	39 100%

Outcome Measures

1. Primary Outcome

Title	The Change in Sleep Continuity From Baseline to Follow-up, as Measured by the Insomnia Severity Index (ISI).
Description	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 ISI (Morin, 1993) was used to assess perceived sleep difficulties or current insomnia symptom severity (i.e., past two weeks). The ISI is a 7-item, self-report instrument with good reliability and validity, and positively correlated with clinician-rated insomnia diagnoses (Bastien, Vallières, & Morin, 2001). Total scores on the full 7-item scale range from 0 - 28 with higher values representing greater sleep continuity disturbance or insomnia severity. The four different treatment groups will be compared for differences.
Time Frame	ISI is measured once at baseline and once at follow-up (8-10 weeks apart)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CBT for Insomnia (CBTI) + Armodafinil	CBTI + Placebo	Armodafinil	Placebo
Arm/Group Description	CBT-I with Armodafinil (active medication) Cognitive Behavioral Therapy for Insomnia: Cognitive Behavioral Therapy for Insomnia. Armodafinil: Active medication	Cognitive Behavioral Therapy for Insomnia with Placebo medication Cognitive Behavioral Therapy for Insomnia: Cognitive Behavioral Therapy for Insomnia. Placebo: Placebo for Nuvigil (armodafinil)	Medication (armodafinil) only, without CBTI. Armodafinil: Active medication	Placebo only, without CBTI. Placebo: Placebo for Nuvigil (armodafinil)
Measure Participants	7	6	6	10
Mean (Standard Deviation) [units on a scale (ISI)]	13.0 (2.1)	17.9 (0.2)	7.7 (0.5)	6 (1.8)

2. Secondary Outcome

Title	Number of Subjects Who Dropped Out
Description	Drop-out rates will be calculated by the number of protocol weeks the subject completed before withdrawing from the study. Drop out rates for subjects taking active v. placebo study medication were compared. Withdrawal indicates subjects who were either lost-to-follow-up (LTFU), chose to withdraw (self-withdrawn), were withdrawn by the study's PI (withdrawn by the investigator).
Time Frame	up to 8 weeks of active study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CBT for Insomnia (CBTI) + Armodafinil	CBTI + Placebo	Armodafinil	Placebo
Arm/Group Description	CBT-I with Armodafinil (active medication) Cognitive Behavioral Therapy for Insomnia: Cognitive Behavioral Therapy for Insomnia. Armodafinil: Active medication	Cognitive Behavioral Therapy for Insomnia with Placebo medication Cognitive Behavioral Therapy for Insomnia: Cognitive Behavioral Therapy for Insomnia. Placebo: Placebo for Nuvigil (armodafinil)	Medication (armodafinil) only, without CBTI. Armodafinil: Active medication	Placebo only, without CBTI. Placebo: Placebo for Nuvigil (armodafinil)
Measure Participants	10	10	8	11
Count of Participants [Participants]	3 30%	4 40%	2 25%	1 9.1%

Adverse Events

Arm/Group Title	CBT for Insomnia (CBTI) + Armodafinil		CBTI + Placebo		Armodafinil		Placebo
Arm/Group Description	CBT-I with Armodafinil (active medication) Cognitive Behavioral Therapy for Insomnia: Cognitive Behavioral Therapy for Insomnia. Armodafinil: Active medication		Cognitive Behavioral Therapy for Insomnia with Placebo medication Cognitive Behavioral Therapy for Insomnia: Cognitive Behavioral Therapy for Insomnia. Placebo: Placebo for Nuvigil (armodafinil)		Medication (armodafinil) only, without CBTI. Armodafinil: Active medication		Placebo only, without CBTI. Placebo: Placebo for Nuvigil (armodafinil)
All Cause Mortality
	CBT for Insomnia (CBTI) + Armodafinil		CBTI + Placebo		Armodafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/8 (0%)		0/11 (0%)
Serious Adverse Events
	CBT for Insomnia (CBTI) + Armodafinil		CBTI + Placebo		Armodafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/8 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	CBT for Insomnia (CBTI) + Armodafinil		CBTI + Placebo		Armodafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/8 (0%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.