Nighttime Agitation and Restless Legs Syndrome in People With Alzheimer's Disease

NCT03082755 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 2016-09-0152R01AG051588-02
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 1

Brief Summary

Nighttime agitation in persons with Alzheimer's disease causes patient suffering, distresses caregivers, and often results in prescriptions for harmful antipsychotics. Effective treatments are lacking because of limited knowledge of the etiology of nighttime agitation. The investigators propose a clinical trial to better elucidate whether a sleep disorder, restless legs syndrome, may be a mechanism for nighttime agitation, and if treatment with gabapentin enacarbil (Horizant®) reduces nighttime agitation, improves sleep, reduces restless legs syndrome behaviors, and reduces antipsychotic medications.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Nighttime Agitation - Cohen Mansfield Agitation Inventory (CMAI) - Direct Observation

  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.

  Change from baseline at 2 and 8 weeks

Secondary Outcomes (5)

• Nighttime Agitation - Cohen Mansfield Agitation Inventory (CMAI) - Caregiver Version.

  Change from baseline at 2 and 8 weeks

• Nighttime Agitation - Modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC).

  Change from baseline at 2 and 8 weeks

• Sleep Disturbance - Direct Observation

  Change from baseline at 2 and 8 weeks

• Sleep Disturbance - Behavioral Indicators Test - Restless Legs (BIT-RL)

  Change from baseline at 2 and 8 weeks

• Sleep Disturbance - Micro-Mini Motionlogger® Actigraph

  Change from baseline at 2 and 8 weeks

Other Outcomes (3)

• Fall Risk and Cognition - Global Rating of Fall Risk (GLORF)

  Change from baseline at 2 and 8 weeks

• Mini-Mental State Examination (MMSE)

  Change from baseline at 2 and 8 weeks

• Physical Mobility Scale (PMS)

  Change from baseline at 2 and 8 weeks

Study Arms (2)

Gabapentin Enacarbil (GEn)

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Gabapentin Enacarbil DRUG

1 to 2 GEn tablets (300 milligrams per tablet) will be administered once a day in the evening (about 5pm) for 8 weeks.

Also known as: Horizant

Gabapentin Enacarbil (GEn)

Placebo Oral Tablet DRUG

1 to 2 Placebo Oral Tablets will be administered once a day in the evening (about 5pm) for 8 weeks.

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged \>=55 years
• Clinical Dementia Rating (CDR) score of 0.5-3, indicating very mild to severe dementia
• Physician diagnosis of dementia of the Alzheimer's type
• Nighttime agitation, defined as Cohen Mansfield Agitation Inventory, Direct Observation total score \>=35
• Opinion of the participant's physician that medication for agitation is appropriate
• RLS diagnosis by study advanced practice nurse (APN) or registered nurse (RN) (in consult with the participant's physician, and the investigators), using the Behavioral Indicators Test-Restless Legs
• Medically stable, defined as unchanged medications within 14 days and the absence of fever or other signs and symptoms of acute illness or delirium (e.g. urinary tract infection, pneumonia) that may cause agitation or interfere with the study protocol
• Able to swallow medication
• Ambulatory, with and without assistance

You may not qualify if:

• Received \>= 50 morphine milligram equivalents per day (MME/d) in the 14 days prior to the randomization decision, because morphine and GEn taken together have a higher incidence of sedation and dizziness than either drug alone
• Currently being treated for RLS with gabapentin or GEn
• Diagnosis of Parkinson's disease (PD) or any other disorder causing tremor because extrapyramidal symptoms may confound RLS diagnosis and actigraphy
• Receiving gabapentin
• Severe psychosis
• Alcohol consumption because combining alcohol and GEn may increase sedation and other adverse events
• Treatment with GEn is contraindicated, such as when a potential participant is receiving multiple antiepileptic drugs, in the opinion of the study APN or RN, participant's physician, or study medical team
• Failure of past treatment with gabapentin or GEn
• Compromised renal function as indicated by creatinine clearance \<15 or on hemodialysis
• Current participation in a clinical trial or in any study that may affect study outcomes
• Determined to be at risk for suicide by the study APN, RN, or participant's physician
• Any condition, that in the opinion of the study APN or RN, participant's physician, or study medical team, makes it medically inappropriate for the patient to enroll in the trial
• Persons living independently in the community without a live-in caregiver (family or hired)

Sponsors & Collaborators

• University of Texas at Austin: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

The University of Texas at Austin

Austin, Texas, 78701, United States

RECRUITING

Related Publications (1)

• Richards K, Morrison J, Wang YY, Rangel A, Loera A, Hanlon A, Lozano A, Kovach C, Gooneratne N, Fry L, Allen R. Nighttime Agitation and Restless Legs Syndrome in Persons With Alzheimer's Disease: Study Protocol for a Double-Blind, Placebo-Controlled, Randomized Trial (NightRest). Res Gerontol Nurs. 2020 Nov 1;13(6):280-288. doi: 10.3928/19404921-20200918-01. Epub 2020 Sep 24.

  PMID: 32966585 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid; Gabapentin

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Kathy Richards, PhD

  The University of Texas at Austin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kathy Richards, PhD

CONTACT

7039463725; kricha@autexas.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The pharmacy, 40 Acres Pharmacy, will maintain records of group assignment. Each participant's assignment will be kept in a separate, unique file uploaded to a UTBox (secure cloud-based file sharing platform) folder created by 40 Acres Pharmacy. Should emergency unmasking be deemed necessary, the Principal Investigator or Co-Investigator will contact the Chief Pharmacist, Forty Acres Pharmacy, who will allow view-only access to the participant's assignment file in UTBox. 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: March 17, 2017
• Study Start: July 1, 2017
• Primary Completion: August 31, 2022
• Study Completion: March 31, 2023
• Last Updated: May 18, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be made available 6 months after publication of the main study findings and will be available in perpetuity.
• Access Criteria: IPD will be publicly available via the following url

Locations

US (1)