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Insomnia and Osteoarthritis Study

Primary Purpose

Osteoarthritis, Insomnia

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Placebo

Eszopiclone

About this trial

This is an interventional treatment trial for Osteoarthritis focused on measuring eszopiclone, insomnia

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age 18-64
Diagnosed with and under physicians care for osteoarthritis of the knee according to American College of Rheumatology Criteria with radiographic evidence demonstrating at least grade 1 osteoarthritis (OA)
Report at least typical arthritic pain>4 out of 10 (0=no pain, 10=the most extreme pain imaginable)
Meet Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and International Classification of Sleep Disorders, Revised definition (ICSD-R) criteria for either primary (psychophysiologic) insomnia or insomnia secondary to osteoarthritis
Insomnia symptoms must include problems with middle of the night awakenings
Insomnia symptom duration > 6 months
Baseline, 2-week, sleep diary average wake after sleep onset time >30 minutes
Baseline self-reported total sleep time < 6.5 hours per night
Patients taking NSAID therapy for pain must be on a stable dose for a period of at least one month prior to initiating the study

Exclusion Criteria:

Intrinsic sleep disorders other than insomnia (sleep apnea, periodic limb movement disorder, etc)
Significant rheumatologic or chronic pain disorders other than osteoarthritis of the knee, including fibromyalgia or the complaint of widespread pain impacting 4 quadrants, complex regional pain syndrome, post herpetic neuralgia, etc)
Major medical disease (including, hepatic impairment, chronic obstructive pulmonary disease/compromised respiratory function, cancer, dementia, diabetes, congestive heart failure, cerebrovascular disease, raynaud's syndrome)
Active major psychiatric disorders (including dementia or cognitive impairment) and history of schizophrenia or bipolar I disorder
History of serious suicide attempt; 6) history of alcohol or substance (including prescription medications) abuse
Pregnancy or plans to become pregnant within 6 months
Intraarticular steroid injection within the past month
Regular (>3 days/week) use of antidepressants, antipsychotics, and mood stabilizers, within the past two months
Regular (> 3/week) use of myorelaxants, narcotics, sedative hypnotics, and anticonvulsants within the past one month
Unwilling or unable to discontinue all use of the medications listed in #10 for two weeks prior to starting the study
Unwilling or unable to discontinue all centrally acting agents and all analgesic usage within 24 hours of pain testing sessions
Refusal to provide consent to contact patient's physician to establish diagnosis and obtain medical record information
Regular tobacco or nicotine use
Heavy caffeine use [(>2 cups of coffee/day (equivalent)
History of previous allergic reaction or severe side effects to sedative hypnotics
Use of potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, troleandomycin, ritonavir, nelfinavir)
In addition, subjects will undergo in-laboratory blood tests prior to receiving drug and will be excluded from further participation if they exhibit: a) positive pregnancy test, b) positive toxicology (benzodiazepine, opioids, Tetrahydrocannabinol (THC), alcohol, and stimulants), c) abnormal liver enzyme panel

Sites / Locations

Johns Hopkins Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Eszopiclone

Placebo

Arm Description

Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks

3mg placebo capsule, once daily at bedtime for 12 weeks

Outcomes

Primary Outcome Measures

Wake After Sleep Onset (WASO)

Total minutes of wakefulness recorded after sleep onset. (Recorded in Daily Sleep Diary) WASO= time awake in the middle of the night, not counting SL or time in bed after awakening. Recorded in minutes

Time in Bed

Total time in bed, in minutes

Sleep Latency (SL)

Sleep Latency: time taken to fall asleep, in minutes (as recorded in daily sleep diary)

Number of Awakenings

As recorded in daily sleep diary

Total Sleep Time (TST)

minutes spent asleep as recorded in daily sleep diary

Sleep Efficiency (SE)

[(TST/ TIB)X 100], (%) as recorded in daily sleep diary

Sleep Quality (SQ)

As recorded in daily sleep diary. Visual analog scales (VAS) Sleep Quality Ratings 0-100, 0= extremely poor sleep quality, (shallow and unrefreshing) and 100=excellent sleep quality (deep and refreshing)

WASO as Assessed by Actigraphy

Subjects wore a Mini Mitter Actiwatch for two continuous weeks at each assessment periods to provide an objective index compared to the assessments made by daily sleep journal. Device is lightweight and worn on non-dominant wrist and contains and omni-directional accelerometer. The accelerometer records the occurrence and degree of motion with a minimal resultant force of .01g. Data are stored as activity counts within a specified epoch. WASO recorded by device = total minutes of wakefulness after sleep onset, in minutes.

TST as Assessed by Actigraphy

Subjects wore a Mini Mitter Actiwatch for two continuous weeks at each assessment periods to provide an objective index compared to the assessments made by daily sleep journal. Device is lightweight and worn on non-dominant wrist and contains and omni-directional accelerometer. The accelerometer records the occurrence and degree of motion with a minimal resultant force of .01g. Data are stored as activity counts within a specified epoch. TST recorded by device = total minutes spent asleep

Sleep Efficiency as Assessed by Actigraphy

Subjects wore a Mini Mitter Actiwatch for two continuous weeks at each assessment periods to provide an objective index compared to the assessments made by daily sleep journal. Device is lightweight and worn on non-dominant wrist and contains and omni-directional accelerometer. The accelerometer records the occurrence and degree of motion with a minimal resultant force of .01g. Data are stored as activity counts within a specified epoch. Sleep efficiency is the index of sleep percentage recorded, equal to total sleep time divided by the time in bed X 100 = X%.

Sleep Latency as Assessed by Actigraphy

Subjects wore a Mini Mitter Actiwatch for two continuous weeks at each assessment periods to provide an objective index compared to the assessments made by daily sleep journal. Device is lightweight and worn on non-dominant wrist and contains and omni-directional accelerometer. The accelerometer records the occurrence and degree of motion with a minimal resultant force of .01g. Data are stored as activity counts within a specified epoch. Sleep latency is the time taken to fall asleep, or equal to lights out- sleep onset (sleep onset: time when sleep is first scored after lights out, first scorable epoch).

Insomnia Severity Index (ISI) Mean Total Scores

The ISI is made up of 7 questions, each possible of earning a score of 0-4, making the total range 0-28, where 0 indicates no severity/no problem with sleep and therefore no insomnia, or 28, being very severe with the highest level of insomnia

Diffuse Noxious Inhibitory Control (DNIC) Index Scores

PPTh:a somedic algometer's 1cm2 rubber probe was placed over muscle belly, with pressure increasing steadily at constant rate (30kPA/Sec), until subject indicated that s/he "first felt pain." PPTh ratings were obtained on right brachioradialis & right trapezius in a random order (average was taken from both areas at each time point). During each cold pressor task, participants immersed contralateral hand (left) up to wrist, in a circulating cold water bath maintained at 4°C. 20 seconds after commencing hand immersion, PPTh was re-assessed on either right brachioradialis or right trapezius (the same site as baseline assessment). After PPTh assessment, participants removed hands from water. DNIC was measured as the % change in PPTh during cold pressor, relative to baseline PPTh [i.e., (mean PPTh during cold pressor / mean PPTh prior to cold pressor)*100]. Increase in PPTh during cold pressor (i.e., percentage scores above 100) reflects normal functioning of pain-inhibitory processes.

Temporal Summation (TS)

TS :maximum windup pain rating - first windup pain rating (0-100). Contact heat stimuli at non tissue damaging temperatures were delivered using computer driven, peltier-element-based stimulator (Medoc, TSA II), with a 9 cm2 probe applied to left forearm. In order to assess temporal summation, three sequences of 10 heat pulses each (with stimulus temperatures of 46 degrees C, 48 degrees C, and 50 degrees C, in random order) were applied to left dorsal forearm. The thermode remains in fixed position during administration of 10 heat pulses that constitute a sequence. Within each sequence, successive thermal pulses at a given temperature are delivered for a duration of approximately 0.5 sec each, with a 2.5-sec inter-pulse interval. The rate of rise & fall of the thermode temp. is set at the device max .of 10 degrees C / S. Subjects verbally rate the perceived intensity of each thermal pulse on a 0-100 rating scale & may terminate the procedure at any time.100=max tolerable intensity

Mean Level of Pain Experienced Throughout the Day

Assessed using a Daily Pain Diary with a scale 0-100, 0 being no pain, 100 being the most severe/intense

Pain as Assessed by the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain Severity Subscale

The WOMAC is a quality of scale life made up of three domains, pain, stiffness, and disability which each comprising of 5, 2, and 7 questions, respectively. A VAS was used for each subscale. Pain was assessed on a scale of 0-100, with 0 being absolutely no pain and 100 being maximum pain.

Secondary Outcome Measures

Heat Pain Threshold

Contact heat stimuli at non tissue damaging temperatures were delivered using computer driven, peltier-element-based stimulator (Medoc, TSA II), with a 9 cm2 probe applied to the left forearm. The thermode was affixed snugly via Velcro straps to ensure even skin contact and repositioned to an adjacent site after each trial to minimize sensitizationHPTh was assessed on the left ventral forearm using an ascending method of limits paradigm; from a non-painful 32°C baseline, the temperature was steadily increased at 0.5°C/sec. Two trials of heat pain threshold were conducted. Averages of both trials are presented from respective time point below. Subjects push a button when the stimulus "first feels painful" The temperature (degrees Celsius) at the time button is pushed is automatically recorded.

Heat Pain Tolerance (HPTOL)

Contact heat stimuli at non tissue damaging temperatures were delivered using computer driven, peltier-element-based stimulator (Medoc, TSA II), with a 9 cm2 probe applied to the left forearm. The thermode was affixed snugly via Velcro straps to ensure even skin contact and repositioned to an adjacent site after each trial to minimize sensitization. HPTOL was assessed on the left ventral forearm using an ascending method of limits paradigm; from a non-painful 32°C baseline, the temperature was steadily increased at 0.5°C/sec. Two trials of HPTOL were conducted. An average of both trials at each respective time point is presented below. Subjects push a button when the stimulus "becomes intolerable." The temperature (degrees Celsius) at the time button is pushed to terminate the stimulation is automatically recorded.

Pressure Pain Threshold

A Somedic algometer was used to assess pressure pain threshold (PPTh) similar to previous studies. The algometer's 1cm2 rubber probe was placed over the muscle belly, with the pressure increased steadily at a constant rate (30kPA/Sec), until the subject indicated that s/he "first felt pain." PPTh was assessed 2 times each, bilaterally, at (in a randomized order) the masseter muscle trapezius muscle, and at the proximal third of the brachioradialis muscle (forearm). The scores from each location were averaged for each participant at that respective time point. The same site was never stimulated consecutively. At least 90 s were maintained between successive stimuli

Quality of Life as Assessed by the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Disability Subscale

The WOMAC is a quality of scale life made up of three domains, pain, stiffness, and disability which each comprising of 5, 2, and 7 questions, respectively. A VAS was used for each subscale. Disability was assessed on a VAS of 0-100, with 0 being absolutely no disability and 100 being maximum disability.

Quality of Life as Assessed by the Short Form-36 (SF-36) Physical Health Component Summary

The SF-36 is a broad, well normed measure of quality of life, comprised of 36 questions aggregated into 8 domains/dimensions. The Physical Component Summary was used here as a global index of physical health functioning. Scale 0-100, with 0 being worst functional level, 100 being the best.

Quality of Life as Assessed by the Short Form-36 (SF-36) Mental Health Component Summary

The SF-36 is a broad, well normed measure of quality of life, comprised of 36 questions aggregated into 8 domains/dimensions. The Mental Component Summary was used here as a global index of mental health functioning. Scale 0-100, with 0 being worst functional level, 100 being the best.

Joint Stiffness as Assessed by the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Joint Stiffness Subscale

The WOMAC is a quality of scale life made up of three domains, pain, stiffness, and disability which each comprising of 5, 2, and 7 questions, respectively. A VAS was used for each subscale. Joint Stiffness was assessed on a VAS scale of 0-20, with 0 being no joint stiffness, and 20 being maximum stiffness.

Full Information

NCT ID

NCT00374556

First Posted

September 8, 2006

Last Updated

March 13, 2019

Sponsor

Johns Hopkins University

1. Study Identification

Unique Protocol Identification Number

NCT00374556

Brief Title

Insomnia and Osteoarthritis Study

Official Title

The Efficacy of Eszopiclone (Lunesta) for Chronic Insomnia Associated With Osteoarthritis.

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

January 2006 (undefined)

Primary Completion Date

December 2013 (Actual)

Study Completion Date

December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Johns Hopkins University

4. Oversight

5. Study Description

Brief Summary

This research is being done to evaluate the effects of a sleeping pill (eszopiclone, Lunesta)in patients with arthritis of the knee who also suffer from chronic insomnia. This study will test whether Lunesta improves sleep, pain sensitivity, and daytime symptoms in patients with knee pain.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Osteoarthritis, Insomnia

Keywords

eszopiclone, insomnia

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Eszopiclone

Arm Type

Experimental

Arm Description

Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

3mg placebo capsule, once daily at bedtime for 12 weeks

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

3mg placebo capsule, once daily at bedtime

Intervention Type

Drug

Intervention Name(s)

Eszopiclone

Intervention Description

3mg capsule, once daily at bedtime

Primary Outcome Measure Information:

Title

Wake After Sleep Onset (WASO)

Description

Time Frame