Nighttime Agitation and Restless Legs Syndrome in People With Alzheimer's Disease
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|ClinicalTrials.gov Identifier: NCT03082755|
Recruitment Status : Recruiting
First Posted : March 17, 2017
Last Update Posted : July 13, 2018
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer Disease||Drug: Gabapentin Enacarbil Drug: Placebo Oral Tablet||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||136 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||The investigators plan to conduct a pilot, 8-week, double-blind, placebo-controlled randomized clinical trial of GEn versus placebo, in 136 nursing home residents with nighttime agitation, RLS, and moderate to severe Alzheimer's Disease. A placebo arm will allow for a thorough and systematic assessment of the safety of GEn in this specific patient population. A 2-month post-trial follow-up will assess whether RLS treatment is continued by providers and antipsychotics are reduced.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||The pharmacy, 40 Acres Pharmacy, will maintain records of group assignment. Sealed envelopes with each participant's assignment for a specific home will also be kept in a secure and locked location in each home that can be accessed only by the registered nurse in charge on each shift. The envelopes will be available in each home in the event that unmasking of assignment is needed during hours when 40 Acres Pharmacy is closed (nights, weekends, holidays). These sealed envelopes may be opened only by physician's order. Participants, their legally authorized representatives and families, participants' physicians, nursing home staff, investigators, and all study personnel will be masked to group assignment. Emergency unmasking of group assignment is expected to be rare. The Data Safety and Monitoring Board will develop guidelines for emergency unmasking.|
|Official Title:||Nighttime Agitation and Restless Legs Syndrome in People With Alzheimer's Disease|
|Actual Study Start Date :||July 1, 2017|
|Estimated Primary Completion Date :||March 31, 2021|
|Estimated Study Completion Date :||March 31, 2022|
Experimental: Gabapentin Enacarbil (GEn)
1 to 2 GEn tablets (300 mg) will be administered by mouth (PO) once a day in the evening (about 5 pm) for 8 weeks then tapered for 1 week. The study drug will be adjusted up to a maximum dosage of 600 mg as tolerated.
Drug: Gabapentin Enacarbil
1 to 2 GEn tablets (300 milligrams per tablet) will be administered once a day in the evening (about 5pm) for 8 weeks.
Other Name: Horizant
Placebo Comparator: Placebo
1 to 2 Placebo Oral Tablet(s) will be administered once a day in the evening (about 5 pm) for 8 weeks then tapered for 1 week. The placebo drug will be adjusted up to a maximum dosage of 2 tablets as tolerated.
Drug: Placebo Oral Tablet
1 to 2 Placebo Oral Tablets will be administered once a day in the evening (about 5pm) for 8 weeks.
Other Name: Placebo
- Nighttime Agitation - Cohen Mansfield Agitation Inventory (CMAI) - Direct Observation [ Time Frame: Change from baseline at 2 and 8 weeks ]The CMAI, modified for direct nighttime observation, will be used to collect objective data on nighttime agitation. Research Assistants (RAs) continuously observe the persons with dementia and record agitation behaviors every 5 minutes. The measure requires that the RAs first note whether the participant is behaviorally awake or asleep. Sleep is defined as a quiet state with eyes closed. Nighttime agitation behaviors are scored during wake. The RA will directly observe the participant when he, or she, is out of bed and record the observations using the CMAI. After the participant has gone to bed, the RA will observe him, or her, via a video camera placed in the bedroom and a small handheld monitor located in a hallway or room adjacent to the bedroom. The monitor will be shielded from view of non-research personnel when on, and turned off between 5-minute observations. The RAs will endeavor to be as sensitive as possible to the privacy of participants.
- Nighttime Agitation - Cohen Mansfield Agitation Inventory (CMAI) - Caregiver Version. [ Time Frame: Change from baseline at 2 and 8 weeks ]The same primary caregivers, if possible, on the evening and night shifts will each complete the CMAI Caregiver Version at baseline and 8 weeks.
- Nighttime Agitation - Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC). [ Time Frame: Change from baseline at 2 and 8 weeks ]The mADCS-CGIC measures clinically meaningful change in the patient's condition relative to baseline on a 7-point Likert scale (markedly worse to markedly improved). The scale was modified to assess items specific to agitation, producing a global rating of change in agitation. This scale will be completed by the study Advanced Practice Nurse (APN) based on physical examination and interviews with nursing home caregivers and persons with dementia (if able).
- Sleep Disturbance - Direct Observation [ Time Frame: Change from baseline at 2 and 8 weeks ]The RA will continuously observe the participant in the evening and night and note every 5 minutes whether the participant is behaviorally awake or asleep. The sleep disturbance outcome will be collected at baseline and 8 weeks. Sleep and wake will be defined as percent of observations asleep or awake on Night 1, 5 pm-10 pm; and Night 2,10 pm-7am. The investigators have chosen to observe on 3 nights at different times to capture any night-to-night and time of night variability in sleep.
- Sleep Disturbance - Behavioral Indicators Test - Restless Legs (BIT-RL) [ Time Frame: Change from baseline at 2 and 8 weeks ]The BIT-RL consists of two parts: 1) Behavioral Indicators - direct observations for RLS behaviors, such as kicking or rubbing legs (8 items), and 2) Clinical Indicators - medical history or family informant interview (3 items), interviews with caregivers (2 items), and an interview with the resident with dementia (1 item). The research assistants (RAs) will continuously observe each participant for RLS behaviors for 20 minutes on one evening, between 6 pm and the usual bedtime. The study APN will assess for the Restless Legs Syndrome Clinical Indicators by reviewing the medical records, and interviewing family members, evening and night shift nurses, and participants. One item, leg discomfort (yes or no) requires an answer from the participant with dementia. The APN will assess for discomfort in legs in the evening during the interval when the evening nurses report that the participant with dementia is most restless.
- Sleep Disturbance - Micro-Mini Motionlogger® Actigraph [ Time Frame: Change from baseline at 2 and 8 weeks ]The micro-mini actigraph is wristwatch-sized accelerometer worn on the wrist. In the investigators' previous studies with over 400 nursing home residents with dementia the investigators have "locked" the actigraph on the participant's wrist with a plastic tie that is comfortable to wear, yet difficult to remove. The actigraph is waterproof and can be left on during showers. Nighttime total sleep time is the main actigraphy sleep outcome. The investigators also will measure other sleep disturbance variables, including nighttime wake after sleep onset, sleep efficiency, sleep latency, and awakenings with the actigraph. Daytime will be defined as 7 am-7 pm, and nighttime will be defined as 7 pm- 7 am. Because the investigators have found that sleep varies in persons with dementia and multiple nights are often needed to obtain a more reliable measure, the investigators will measure sleep for 7 days and nights at baseline and 7 days and nights at 8 weeks.
- Fall Risk and Cognition - Global Rating of Fall Risk (GLORF) [ Time Frame: Change from baseline at 2 and 8 weeks ]This is a single question measure: "How do you judge the risk that Mr. or Mrs. X will fall within 6 months - high or low?" asked at baseline, week 2, and week 8 of a nurse or aide with personal knowledge of the resident. If possible, the same nurse, aide, or caregiver will complete the GLORF each week.
- Mini-Mental State Examination (MMSE) [ Time Frame: Change from baseline at 2 and 8 weeks ]The MMSE (range 0-30) is a 30-item cognitive screen measuring orientation, registration, short-term memory, attention/concentration, language and constructional capacity. The MMSE is a widely used screening test of cognition and takes about 10 minutes to administer to the person with dementia.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03082755
|Contact: Janet D Morrison, PhD||512 471 firstname.lastname@example.org|
|United States, Texas|
|The University of Texas at Austin||Recruiting|
|Austin, Texas, United States, 78701|
|Contact: Janet D Morrison, PhD 512-965-4023 email@example.com|
|Contact: Kathy Richards, PhD 7039463725 firstname.lastname@example.org|
|Principal Investigator:||Kathy Richards, PhD||The University of Texas at Austin|
|Principal Investigator:||Christine Kovach, PhD||University of Wisconsin, Milwaukee|