Sleep in Osteoarthritis Project

Sleep disturbance and pain are two of the most common and disabling symptoms of OA. Sleep
disturbances have been shown to worsen clinical pain by impairing some of the body's central
pain processing mechanisms. Sufficient research is lacking, however, on what treatments may
be effective for sleep disturbance in people with OA or whether normalization of sleep
patterns in people with OA will reduce their pain. This study will evaluate the effectiveness
of behavioral treatments for insomnia in reducing sleep disturbances, thereby reducing
clinical pain in people with knee OA.

Participants in Phase 1 of this study will be separated into the following four groups:
people with OA and insomnia; people with OA, but without insomnia; people without OA, but
with insomnia; and people without OA or insomnia. All participants will attend two study
visits. During Visit 1, participants will complete questionnaires and an interview and will
provide a urine sample and a set of recent x-rays. A diary, which will be used to record
activity levels for 2 weeks, will also be given to all participants.

Optional Ancillary Sleep and Immunoreactivity Study Procedures

Subjects who pass the visit one screen will be provided the option of participating in
ancillary study procedures designed to assess inflammatory biomarkers present in plasma,
physical functioning capabilities, and pain and mood status during the pain testing
procedures. Subjects will be asked to give blood samples during the pain testing procedures,
followed by standardized tests of physical function. Subjects will be also asked to complete
additional questionnaire and diary items that ask them to rate their emotions during the pain
testing procedures and during the days that they keep their electronic diary for the parent
project. At Visit 2, participants will undergo pain testing, an in-home sleep study and
optional procedures outlined above. At Visit 3, participants with knee osteoarthritis will
have an exam by a rheumatologist.

Participants in Phase 1 who have both knee OA and insomnia will be asked to continue into
Phase 2, which will last 8 months. These participants will be randomly assigned to receive
two different forms of behavioral treatment, cognitive behavior therapy (CBT) or a behavioral
desensitization treatment. Participants assigned to both treatments will meet with a
psychologist once a week for 8 weeks. Participants will learn new sleeping habits and mental
exercises designed to reduce arousal and alertness while trying to sleep. All participants
will attend four assessment visits over the course of Phase 2. The first visit will occur at
Week 4 and will include completing questionnaires and undergoing pain testing. The second
visit will occur at Week 8 and will include the same questionnaires, further pain testing
with optional blood draws and physical tests and an in-home sleep study. Two weeks before
assessment Visit 3, participants will receive a diary in the mail, which they will use to
keep track of their pain, sleep, medications, and symptoms until Visit 3. Assessment Visit 3
will take place at Month 5 and will include the same procedures followed during Visit 2.
Participants will complete a second diary 2 weeks before Visit 4. At Visit 4, which will
occur at Month 8, the same procedures completed at Visits 2 and 3 will be repeated.

Inclusion Criteria:

For all participants:

- Age ≥ 50 ; or 35 ≥ if KOA/Insomnia group

For participants with knee OA:

- Meets American College of Rheumatology (ACR) criteria for knee OA

- Shows radiographic evidence of Kellgren-Lawrence Grade OA greater than or equal to 1

- Experiences knee pain more than 5 days per week for more than 6 months

- Reports at least typical arthritic pain (a score of at least 2 out of 10, with 0 being
no pain and 10 being the most extreme pain imaginable)

- Patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen must
be on a stable dose for at least 1 month prior to study entry

- Not scheduled for arthroplasty or surgery during projected period of study
participation

For participants with insomnia:

- A sleep maintenance insomnia profile is evident both at study entry (based on
retrospective reports) and as an average profile from 2 weeks of sleep diaries

- Meets diagnostic criteria for insomnia due to knee OA only or for primary insomnia

- Reports total sleep time less than 6.5 hours

- Middle insomnia symptom frequency of more than 3 nights per week for more than 1 month

For participants without insomnia:

- Meets research diagnostic criteria for normal sleepers

- Insomnia Severity Index of less than 10

- Epworth Sleepiness score of less than 10

- Pittsburgh Sleep Quality Index score of less than 5

- Wake After Sleep Onset Time is under 30 minutes

- Sleep efficiency percentage is greater than 85%

- Total sleep time is greater than 6.5 hours

For participants without knee OA and without insomnia:

- Free from any acute pain or injury

- No recent history of chronic pain within 3 years prior to study entry (pain severity
report greater than 2 out of 10 more than 2 days per week for 6 months)

- Reports good overall health, with no major medical or psychiatric illness known to
disturb sleep or cause pain

Exclusion Criteria:

- Sleep disorders other than insomnia (e.g., obstructive sleep apnea, periodic limb
movement disorder, etc.)

- Apnea/Hypopnea Index (AHI) of greater than 15

- Significant rheumatologic or painful disorders other than knee OA (including
fibromyalgia, rheumatoid arthritis, neuralgia, etc.)

- Any major medical diseases known to impact sleep or cause pain (including chronic
obstructive pulmonary disease, diabetes, congestive heart failure, seizure disorder,
Raynaud's phenomenon, etc.)

- Dementia or cognitive impairment, defined as Mini Mental State Exam score of less than
24

- Current or recent history of major psychiatric disorders (within 3 months prior to
study entry)

- History of schizophrenia or bipolar I disorder

- Center for Epidemiologic Studies of Depression Scale (CES-D) greater than or equal to
27 or suicidal ideation

- Current or history of substance abuse (within 6 months prior to study entry)

- Use of antidepressants, antipsychotics, or mood stabilizers more than 3 days per week
in the past 2 months- Note: only applies to groups other than KOA/Insomnia

- Use of narcotics (opioids), myorelaxants, sedatives, or anticonvulsants more than 3
days per week within 1 month prior to study entry

- Unwilling or unable to discontinue all use of certain medications by 1 week prior to
study entry

- Refuses to contact physician to obtain relevant medical record information

- Pregnancy or plans to become pregnant within 6 months

- Positive toxicology test (benzodiazepines and receptor agonists, barbiturates,
opioids, tetrahydrocannabinol, alcohol, and stimulants)