Mild Cognitive Impairment and Obstructive Sleep Apnea (MEMORIES)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by George Mason University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Kathy C. Richards, George Mason University
ClinicalTrials.gov Identifier:
NCT01482351
First received: November 28, 2011
Last updated: March 8, 2012
Last verified: March 2012
  Purpose

The goal of the research is to determine the power and the feasibility of the study design and methods to inform a full-scale clinical trial that will determine whether treatment of obstructive sleep apnea in older adults with mild cognitive impairment delays cognitive decline and preserves everyday function.


Condition Intervention Phase
Obstructive Sleep Apnea
Mild Cognitive Impairment
Device: Continuous Positive Airway Pressure [CPAP]
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: Mild Cognitive Impairment and Obstructive Sleep Apnea

Resource links provided by NLM:


Further study details as provided by George Mason University:

Primary Outcome Measures:
  • Hopkins Verbal Learning Test-Revised [HVLT-R] [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]
    Memory (immediate and delayed recall) will be assessed using HVLT-R. HVLT-R has been used in elders with Alzheimer's Disease and takes 10 minutes to complete. We will use 6 alternative forms. Forms 1, 2, and 4 will be used for half the participants and forms 3, 5 and 6 will be used for the rest of the participants.

  • Everyday Cognition [E-Cog] [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]
    Cognitively mediated functional abilities will be assessed using E-Cog. It is a study-partner rated 39-item questionnaire.


Secondary Outcome Measures:
  • Digit Symbol-Coding [DSC] [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]
    Psychomotor/cognitive processing speed will be assessed using the DSC subtest from the Wechsler Adult Intelligence Test (WAIS-III).

  • Mini Mental State Exam (MMSE) [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]
    Global cognitive function will be assessed using MMSE. It is a 30-item cognitive screen measuring orientation, registration, short-term memory, attention/concentration, language, and constructional capacity. Summary score will be used as a measure of global cognitive function. It takes about 5 minutes to complete.

  • Stroop Color and Word Test [SCW] [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]
    Attention will be measured using SCW. We will use the Golden format, which is sensitive to age-related declines in processing speed. The SCW has been used in elders with Alzheimer's Disease and it takes about 30 minutes to complete.

  • The Psychomotor Vigilance Task (PVT) [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]
    Attention/reaction time will assessed using the PVT. PVT has been used in elders with Alzheimer's Disease and requires about 30 minutes to complete.

  • Epworth Sleepiness Scale [ESS] [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]
    Daytime sleepiness be assessed using ESS. The ESS asks the respondent to rate the likelihood of falling asleep in eight specific situations using a four-point Likert scale ranging from never dozing to high chance of dozing. The scale significantly correlates with the frequency of apneas and is a clinical and research standard for the assessment of daytime sleepiness. Persons with cognitive impairment are able to complete the scale. It requires 5 minutes to complete.

  • Functional Outcomes Sleep Questionnaire [FOSQ] [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]
    Everyday function will be assessed using FOSQ. It is a 30-item Likert-scale, self-report, disease-specific functional status measure written at the 4th grade level.

  • Alzheimer's Disease Cooperative Study - Clinicians' Global Impression of Change Scale [ADCS-CGIC] [ Time Frame: Change from baseline at 1 year for the active arm ] [ Designated as safety issue: No ]
    Global change (progression) will be assessed using ADCS-CGIC at 1 year. It can be completed at home by participants or their study partners. It is sensitive to small differences in several domains that may add up to a clinically meaningful change.

  • Clinical Dementia Rating Scale [CDR] [ Time Frame: Change from baseline at 1 year for the active arm ] [ Designated as safety issue: No ]
    Cognitive ability will be assessed and staged using CDR. It uses a structured interview takes 60-90 minutes to complete. The CDR will be completed by the graduate assistant with input from the geriatrician and neuropsychologist.

  • Neuroimaging Biomarker: Hippocampal Volume [ Time Frame: Change in hippocampal volume between baseline and 1 year follow-up magnetic resonance imaging scan. ] [ Designated as safety issue: No ]
    Change in hippocampal volume between baseline and 1 year follow-up scan (atrophy) will be quantified automatically using unbiased registration between 2 time points. Structural and calibration scans used in this protocol have been adopted from the Alzheimer's Disease Neuroimaging Initiative [ADNI] protocol.

  • Neuroimaging Biomarker: Regional Brain Volume and Thickness. [ Time Frame: Change in regional brain volume and thickness between baseline and 1 year follow-up magnetic resonance imaging scan. ] [ Designated as safety issue: No ]
    Structural effects of CPAP outside of the hippocampus will be measured using FreeSurfer software to automatically estimate hemispheric and lobar cortical thickness; cortical and subcortical gray matter volume; white matter volume; and ventricular volume. The FreeSurfer longitudinal module will be used to estimate change in these measures.

  • Neuroimaging Biomarker: Hippocampal Subfield Volumes. [ Time Frame: Change in hippocampal subfield volume between baseline and 1 year follow-up magnetic resonance imagingscan. ] [ Designated as safety issue: No ]
    We will perform automatic segmentation of hippocampal subfields in the baseline T2-weighted turbo spin echo [TSE] images. This will estimate volumes of subfields CA1, CA2, CA3, dentate gyrus, subiculum, and entorhinal cortex. We will then quantify longitudinal change in subfield volumes using the approach for the whole hippocampus, modified to account for anisotropic voxel size in TSE images.

  • Neuroimaging Biomarker: Ischemic Lesion Volume. [ Time Frame: Change in ischemic lesion volume between baseline and 1 year follow-up magnetic resonance imaging scan. ] [ Designated as safety issue: No ]
    The volume of white matter hyperintensity (leuokoaraiosis) will be assessed in CSFsuppressed T2-weighted (FLAIR) structural MRI. A semi-automated intensity-based segmentation technique will be used to identify cortical and subcortical strokes as well as ischemic lesions in subcortical white matter considered to be the sequelae of hypoperfusion.

  • Neuroimaging Biomarker: Cerebral Blood Flow. [ Time Frame: Change in cerebral blood flow between baseline and 1 year follow-up magnetic resonance imaging scan. ] [ Designated as safety issue: No ]
    ASL perfusion MRI provides regional cerebral blood flow (rCBF) in absolute units of ml/100g/min. Arterial Spin Labeling [ASL] signal processing will follow established procedures in our laboratory using the ASL data processing toolbox (ASL tbx). CBF will then be quantified within cortical gray matter, hippocampal gray matter, and white matter regions based on FreeSurfer templates.


Estimated Enrollment: 110
Study Start Date: February 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sham Comparator: Sham Continuous Positive Airway Pressure Device: Continuous Positive Airway Pressure [CPAP]
Study participants will be randomized to receive either active continuous positive airway pressure (CPAP) or sham CPAP for 6 months. Dosage of active CPAP will be individually determined using standardized methods in an overnight CPAP titration polysomnography. At the end of 6 months those in the sham group will receive active CPAP and be discharged from the study. Those assigned to the active CPAP group will participate in an open label study for 6 additional months.
Active Comparator: Active Continuous Positive Airway Pressure Device: Continuous Positive Airway Pressure [CPAP]
Study participants will be randomized to receive either active continuous positive airway pressure (CPAP) or sham CPAP for 6 months. Dosage of active CPAP will be individually determined using standardized methods in an overnight CPAP titration polysomnography. At the end of 6 months those in the sham group will receive active CPAP and be discharged from the study. Those assigned to the active CPAP group will participate in an open label study for 6 additional months.

Detailed Description:

We propose to conduct a 6-month double-blind randomized, placebo-controlled pilot clinical trial to compare the effects of active continuous positive airway pressure versus sham continuous positive airway pressure on cognitive and everyday function in 110 older adults with mild cognitive impairment and obstructive sleep apnea. We also will collect pilot data on the 1-year outcomes of treatment of obstructive sleep apnea, and the validity of neuroimaging for measuring clinical change in persons with mild cognitive impairment and obstructive sleep apnea. The results will inform the study design, sample size, participant recruitment and retention methods, and measures for a full-scale trial.

  Eligibility

Ages Eligible for Study:   55 Years to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Participants are included in the study if all of the following criteria are met:

  • Are able to provide written informed consent by self or legally authorized representative. MacArthur Competency Assessment Tool [MacCAT-CR] will be used to assess decision making capacity
  • Moderate to severe obstructive sleep apnea (OSA) as defined by an apnea-hypopnea index (AHI) >= 15 using either the Apnea Risk Evaluation System (ARES) OR diagnostic polysomnography as a screening measure
  • Scoring < = 11 on Dementia Severity Rating Scale
  • Scoring education-adjusted total scores < 26 on Montreal Cognitive Assessment
  • Scoring education adjusted scores 28-35 (inclusive) on Telephone Interview for Cognitive Status Modified
  • Permitted medications stable for at least 4 weeks
  • Scoring less than or equal to14 on the Beck Depression Inventory II (BDI-II) 21-item scale (i.e., non-depressed)
  • Having a study partner, defined as an informant/caregiver who has an average of 10 hours per week or more contact with and accompanies participant to most study visits
  • Adequate visual and auditory acuity to allow testing
  • Women must be surgically sterile, 2 years postmenopausal
  • Testability - willing and able to complete baseline, 6-month, and 1-year outcome measures, and willing to send in the CPAP Smartcard for adherence
  • Willing to undergo magnetic resonance imaging (MRI) and provide DNA for ApoE4 assessments
  • Completed at least 6 grades of education or had a good work history inside or outside the home (to exclude mental retardation)
  • Fluent in English.

Exclusion criteria:

Patients are excluded from participating in this study if 1 or more of the following criteria are met:

  • Any significant neurologic disease other than MCI, such as Parkinson's Disease, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defects or known structural brain abnormalities
  • Any MRI exclusions - presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin, or body
  • Psychiatric disorders, including major depression or bipolar disorder based on DSM-IV diagnostic criteria within the past 3 months, psychotic features, agitation or behavioral problems within the last 3 months that could lead to difficulty complying with the protocol, or history of schizophrenia (also by DSM-IV criteria)
  • History of alcohol abuse or dependence within the past 2 years (DSM-IV criteria)
  • Any current significant systemic illness or unstable medical condition that could lead to difficulty in complying with the protocol (bronchospasm or symptomatic chronic obstructive pulmonary disease as indicated by regular use of bronchodilators, steroids, history of carbon dioxide retention, waking hypoxemia, or use of supplemental oxygen; uncontrolled thyroid disease, diabetes, or seizure disorder; cirrhosis; recently diagnosed cancer; clinically significant laboratory abnormalities such as B12)
  • Any current known conditions that may increase short-term risk from untreated OSA: symptomatic coronary or cerebrovascular disease as indicated by recent myocardial infarction or stroke (6 months), congestive heart failure (New York Heart Classification stage 3), unstable angina, life-threatening arrhythmias, cardiomyopathy, transient ischemic attacks and history of driving accidents related to daytime sleepiness
  • Participating in clinical studies involving neuropsychological measures being conducted more than twice a year or another clinical trial
  • Currently receiving CPAP or bi-level pressure for OSA; and
  • Requires oxygen or bi-level pressure during CPAP titration polysomnography
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01482351

Contacts
Contact: Kathy Richards, PhD, RN 7039931961 kricha11@gmu.edu

Locations
United States, Pennsylvania
Abington Memorial Hospital Recruiting
Abington, Pennsylvania, United States, 19001
Contact: Mary T Hofmann, MD    215-481-4350    MHofmann@amh.org   
Principal Investigator: Mary T Hofmann, MD         
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Nalaka Gooneratne, MD    215-349-5938    ngoonera@mail.med.upenn.edu   
Principal Investigator: Nalaka Gooneratne, MD         
United States, Virginia
George Mason University Recruiting
Fairfax, Virginia, United States, 22030
Contact: Kathy C Richards, PhD, RN, FAAN    703-993-1962    kricha11@gmu.edu   
Principal Investigator: Kathy C Richards, PhD, RN, FAAN         
Sponsors and Collaborators
George Mason University
Investigators
Principal Investigator: Kathy Richards, PhD, RN George Mason University
  More Information

No publications provided

Responsible Party: Kathy C. Richards, University Professor and Assistant Dean Doctoral Programs and Research Development, George Mason University
ClinicalTrials.gov Identifier: NCT01482351     History of Changes
Other Study ID Numbers: 7584, R01AG034682-01A2
Study First Received: November 28, 2011
Last Updated: March 8, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by George Mason University:
apnea
cognition
memory
function
amnestic mild cognitive impairment
older adults
Alzheimer's Disease

Additional relevant MeSH terms:
Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Cognition Disorders
Mild Cognitive Impairment
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on October 16, 2014