Clinical trial NCT00711516: Study to Evaluate Armodafinil Treatment in Improving Prefrontal Cortical Activation and Working Memory Performance
Official title: Double-Blind, Placebo-Controlled, Functional Neuroimaging Study of Armodafinil (200 mg/Day) on Prefrontal Cortical Activation in Patients With Residual Excessive Sleepiness Associated With Obstructive Sleep Apnea/Hypopnea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Excessive Sleepiness
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2008-07-09
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine whether treatment with armodafinil will provide improvements in prefrontal cortical activation in patients with OSAHS (Obstructive Sleep Apnea/Hypopnea Syndrome) who have residual sleepiness despite receiving nCPAP therapy.


Eligibility criteria: Inclusion Criteria:

* Patient has a current diagnosis of OSAHS and has a complaint of excessive sleepiness despite effective nCPAP therapy.
* Patient has excessive sleepiness as evidenced by a mean sleep latency of less than 8 minutes, as determined by the MSLT.
* Patient has an ESS score of 10 or more at the initial screening visit.
* Patient has a habitual sleep time beginning no earlier than 2100 and ending no later than 0700.
* Patient is right-handed. Patients who are ambidextrous may be eligible following consultation with the medical monitor.
* Women of childbearing potential must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study.
* Patient exhibits reasonable accuracy (≥80%) on the 2-back working memory task during the training session at the second screening visit.

Exclusion Criteria:

The Patient:

* The patient is a current smoker or has a prior history of smoking (defined as ≥1 pack-year) within 2 years prior to the screening visit.
* consumes caffeine including coffee, tea and/or other caffeine-containing beverages or food averaging more than 400 mg of caffeine per day (approximately equivalent to 4 or more cups of coffee).
* has NART-predicted verbal IQ and QIDS-SR16 scores within protocol-specific exclusionary ranges.
* has a clinically significant, uncontrolled medical or psychiatric conditions (treated or untreated).
* has a confirmed or probable diagnosis of a current sleep disorder other than OSAHS.
* has used any excluded prescription drugs or procedures for prohibited and allowed drugs within the excluded timeframe.
* has a history of alcohol, narcotic, or any other drug abuse.
* has a positive UDS, without medical explanation, at the screening visit.
* has a clinically significant deviation from normal in the physical examination.
* is a pregnant or lactating woman. Any woman becoming pregnant during the study will be withdrawn from the study.
* has a past or present seizure disorder, head trauma that is clinically significant, or past neurosurgery.
* has used an investigational drug within 1 month before the screening visit.
* has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery).
* has a known hypersensitivity to armodafinil or modafinil, or any other component of the study drug tablets.
* has a history of any clinically significant cutaneous drug reaction, or a history of clinically significant hypersensitivity reaction, including multiple allergies or drug reactions.
* has known human immunodeficiency virus (HIV).
* has clinical laboratory test value(s) outside the range(s) specified in the Protocol, or presents a clinically significant laboratory abnormality without prior written approval by the medical monitor.
* has worked the night shift within 28 days of the baseline visit, or will work the night shift during the double-blind segment of the study.
* anticipates any travel across more than 3 time zones at any time during the study.
* needs to use any of the excluded medications identified in this protocol.
* is unable to complete neuroimaging studies, performance tasks, self-rating scales, and all other study assessments.
* has a contraindication to fMRI scanning, (such as an implanted pacemaker/defibrillator, aneurysm clips, drug infusion device or metallic foreign body).
* is suspected to be unable to tolerate fMRI scanning (eg, claustrophobic) and/or the testing paradigm.
* has physical or other characteristics that suggest imaging data will be unobtainable or degraded.

Primary outcomes:
measure: Change From Baseline to Endpoint in Number of Contiguous Activated Voxels Meeting Predefined Threshold in Dorsolateral Prefrontal Cortex (DLPFC) on Functional Magnetic Resonance Imaging (fMRI) as a Measure of Prefrontal Cortical Activation
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
Secondary outcomes:
measure: Change From Baseline to Endpoint in Mean Response Latency in the 2-Back Working Memory Test at Endpoint - Mean Performance Speed
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Change From Baseline to Endpoint in the Number of Contiguous Activated Voxels Meeting the Predefined Threshold in the Anterior Cingulate Cortex (ACC)
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Change From Baseline to Endpoint in the Number of Contiguous Voxels Meeting the Predefined Threshold in the Posterior Parietal Cortex (PPC)
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Change From Baseline to Endpoint in the Number of Contiguous Activated Voxels Meeting the Predefined Threshold in the Thalamus
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Pattern Recognition Memory (PRM) Percent Correct (Immediate) From the CANTAB Battery-Change From Baseline to Endpoint
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Pattern Recognition Memory (PRM) Percent Correct (Delayed) From the CANTAB Battery-Change From Baseline to Endpoint
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Reaction Time Index (RTI) Median Correct Latency, Five Choice Test From the CANTAB Battery-Change From Baseline to Endpoint
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Reaction Time Index (RTI) Median Correct Latency, One Choice Test From the CANTAB Battery-Change From Baseline to Endpoint
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: One Touch Stockings of Cambridge (OTS) Mean Correct Latency, (Easy) From the CANTAB Battery-Change From Baseline to Endpoint
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: One Touch Stockings of Cambridge (OTS) Mean Correct Latency, (Hard) From the CANTAB Battery-Change From Baseline to Endpoint
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: One Touch Stockings of Cambridge (OTS) Mean Choices to Correct, (Easy) From the CANTAB Battery-Change From Baseline to Endpoint
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: One Touch Stockings of Cambridge (OTS) Mean Choices to Correct, (Hard) From the CANTAB Battery-Change From Baseline to Endpoint
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Epworth Sleepiness Scale Change From Baseline to Endpoint
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Clinical Global Impression of Change (CGI-C)- Number of Responders at Endpoint
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Total Score From the Medical Outcomes Study 6-Item Cognitive Function Scale (MOS-CF6)-Change From Baseline to Endpoint
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Blood Oxygenation Level Dependent (BOLD) Signal Intensity - Percent Change From Baseline to Endpoint in the Dorsolateral Prefrontal Cortex (DLPFC)
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Blood Oxygenation Level Dependent (BOLD) Signal Intensity - Percent Change From Baseline to Endpoint in the Anterior Cingulate Cortex (ACC)
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Blood Oxygenation Level Dependent (BOLD) Signal Intensity -Change From Baseline to Endpoint in the Posterior Parietal Cortex (PPC)
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Blood Oxygenation Level Dependent (BOLD) Signal Intensity - Percent Change From Baseline to Endpoint in the Thalamus
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Activation-Performance Relationship Between the Functional Magnetic Resonance Imaging (fMRI) in Dorsolateral Prefrontal Cortex (DLPFC) and 2-Back Working Memory Test - Number of Voxels Activated at Endpoint
timeFrame: Endpoint (Week 2 or last observation after baseline)
measure: Activation-Performance Relationship Between the Functional Magnetic Resonance Imaging (fMRI) in Anterior Cingulate Cortex (ACC) and 2-Back Working Memory Test - Number of Voxels Activated at Endpoint
timeFrame: Week 2 or Last Observation after Baseline
measure: Activation-Performance Relationship Between Functional Magnetic Resonance Imaging (fMRI) in Posterior Parietal Cortex (PPC) and the 2-Back Working Memory Test -Number of Voxels Activated at Endpoint
timeFrame: Week 2 or Last Observation after Baseline
measure: Activation-Performance Relationship Between Functional Magnetic Resonance Imaging (fMRI) in the Thalamus and 2-Back Working Memory Test -Number of Voxels Activated at Endpoint
timeFrame: Week 2 or Last Observation after Baseline
measure: Activation-Performance Relationship Between the Functional Magnetic Resonance Imaging (fMRI) in Dorsolateral Prefrontal Cortex (DLPFC) and 2-Back Working Memory Test - Blood Oxygen Level Dependent (BOLD) Signal Intensity at Endpoint
timeFrame: Week 2 or Last Observation after Baseline
measure: Activation-Performance Relationship Between Functional Magnetic Resonance Imaging (fMRI) in Anterior Cingulate Cortex (ACC) and 2-Back Working Memory Test -Blood Oxygen Level Dependent (BOLD) Signal Intensity at Endpoint
timeFrame: Week 2 or Last Observation after Baseline
measure: Activation-Performance Relationship on Functional Magnetic Resonance Imaging (fMRI) in Posterior Parietal Cortex (PPC) and 2-Back Working Memory Test - Blood Oxygen Level Dependent (BOLD) Signal Intensity at Endpoint
timeFrame: Week 2 or Last Observation after Baseline
measure: Activation-Performance Relationship on Functional Magnetic Resonance Imaging (fMRI) in the Thalamus and 2-Back Working Memory Test - Blood Oxygen Level Dependent (BOLD) Signal Intensity at Endpoint
timeFrame: Week 2 or Last Observation after Baseline
measure: Number of Contiguous Activated Voxels Meeting Predefined Threshold in the DLPFC on fMRI on the 2 Back Working Memory Test - Change From Baseline-Subgroup-Responders in 2 Back Working Memory Test
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Number of Contiguous Activated Voxels Meeting Predefined Threshold in the ACC on fMRI by 2-Back Working Memory Test -Change From Baseline; Subgroup-Responders in 2 Back Memory Test
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Number of Contiguous Activated Voxels Meeting Predefined Threshold in the PPC on fMRI by 2-Back Working Memory Test-Change From Baseline; Subgroup-Responders in 2 Back Memory Test
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Number of Contiguous Activated Voxels Meeting Predefined Threshold in the Thalamus on fMRI by 2-Back Working Memory Test-Change From Baseline; Subgroup-Responders in 2 Back Memory Test
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Number of Contiguous Activated Voxels Meeting Predefined Threshold in the DLPFC on fMRI by 2-Back Working Memory Test-Change From Baseline; Subgroup-Non Responders in 2 Back Memory Test
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Number of Contiguous Activated Voxels Meeting Predefined Threshold in the ACC on fMRI by 2-Back Working Memory Test-Change From Baseline; Subgroup-Non Responders in 2 Back Memory Test
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Number of Contiguous Activated Voxels Meeting Predefined Threshold in the PPC on fMRI by 2-Back Working Memory Test-Change From Baseline; Subgroup-Non Responders in 2 Back Memory Test
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Number of Contiguous Activated Voxels Meeting Predefined Threshold in the Thalamus on fMRI by 2-Back Working Memory Test-Change From Baseline; Subgroup-Non Responders in 2 Back Memory Test
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Change From Baseline to Endpoint in the BOLD Signal Intensity in the Dorsolateral Prefrontal Cortex (DLPFC) at Resting State
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Change From Baseline to Endpoint in the BOLD Signal Intensity in the Anterior Cingulate Cortex (ACC) at Resting State
timeFrame: Baseline and Endpoint (Week 2 or last observation after Baseline)
measure: Change From Baseline in the BOLD Signal Intensity in the Posterior Parietal Cortex (PPC) at Resting State
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Change From Baseline to Endpoint in the BOLD Signal Intensity in the Thalamus at Resting State
timeFrame: Baseline and Endpoint (Week 2 or last observation after Baseline)
measure: Change From Baseline to Endpoint in the Number of Voxels Meeting Predefined Threshold in the Dorsolateral Prefrontal Cortex (DLPFC) at Resting State
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Change From Baseline to Endpoint in the Number of Voxels Meeting Predefined Threshold in Anterior Cingulate Cortex (ACC) at Resting State
timeFrame: Baseline and Endpoint (Week 2 or last observation after Baseline)
measure: Change From Baseline to Endpoint in the Number of Voxels Meeting Predefined Threshold in Posterior Parietal Cortex (PPC) at Resting State
timeFrame: Baseline and Endpoint (Week 2 or last observation after Baseline)
measure: Change From Baseline to Endpoint in the Number of Voxels Meeting Predefined Threshold in the Thalamus at Resting State
timeFrame: Baseline and Endpoint (Week 2 or last observation after baseline)
measure: Change From Baseline to Endpoint (2 Weeks or Last Observation After Baseline) in the Mean Response Latency in the Psychomotor Vigilance-Like Test
timeFrame: Baseline and Endpoint (Week 2 or last observation after Baseline)
Other outcomes:
Locations:
city: Burlingame
country: United States
facility: Peninsula Sleep Center
state: California
city: San Diego
country: United States
facility: Pacific Research
state: California
city: San Diego
country: United States
facility: VA San Diego Healthcare System
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Boston
country: United States
facility: Beth Israel Deaconess Medical
state: Massachusetts
city: Newton
country: United States
facility: Neurocare, Inc.
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
Study officials:
affiliation: Cephalon
name: Sponsor's Medical Expert
role: STUDY_DIRECTOR
References:
citation: Greve DN, Duntley SP, Larson-Prior L, Krystal AD, Diaz MT, Drummond SP, Thein SG, Kushida CA, Yang R, Thomas RJ. Effect of armodafinil on cortical activity and working memory in patients with residual excessive sleepiness associated with CPAP-Treated OSA: a multicenter fMRI study. J Clin Sleep Med. 2014 Feb 15;10(2):143-53. doi: 10.5664/jcsm.3440.