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Alzheimer DiseasePhase 4ADADNCT00417482

Antipsychotic Discontinuation in Alzheimer's Disease

A Phase 4 study testing risperidone in people with Alzheimer Disease and Psychotic Disorders, run by New York State Psychiatric Institute at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

In patients with Alzheimer's disease (AD) who respond to antipsychotic treatment of psychosis and/or agitation/aggression, the relapse risk after discontinuation is not established. AD patients with psychosis and/or agitation/aggression receive 16 weeks of open risperidone treatment (Phase A). Read more about this study

Who is it for?
Ages 50 to 95 years
Conditions the study is for
Alzheimer Disease, Psychotic Disorders, Agitation
What is being tested?
risperidone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
180 participants
Where
7 sitesUnited States
Study dates
Aug 2004to Apr 2011
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 95 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Dementia, either sex, age 50-95 years
  • Probable Alzheimer's disease
  • Intellectual impairment present for at least 6 months
  • Mini Mental State Exam (MMSE) score of 5-26 for outpatients and 2-26 for nursing home patients
  • Availability of informant who has had direct contact with the patient for an average of at least once every week during the 3 months prior to study entry
  • Meets Neuropsychiatric Inventory (NPI) criteria for either (1) psychosis, or (2) agitation/aggression
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  • Able to mobilize independently (if wheelchair-bound, the patient must be able to self-propel)
  • Free of psychotropic medication (or able to tolerate washout) for at least 1 week prior to study entry. Low dose antidepressants and sedative/hypnotics allowed if they cannot be washed out and the dose remains stable for the study duration
  • Expected to complete the study (including all efficacy evaluations) and be without major sensory impairment that would prevent participation in any aspect of the study

Who cannot join

  • Current primary Axis I psychiatric disorder other than AD
  • Substance abuse or dependence currently, or within the past year
  • Dementia due to head trauma
  • History of allergy to risperidone or intolerance to risperidone
  • Diffuse Lewy body disease
  • History of seizure disorder, infectious encephalitis, Parkinson's disease, central nervous system (CNS) neoplasm, tardive dyskinesia, stroke, transient ischemic attack (TIA) or uncontrolled atrial fibrillation
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  • Use of monoamine oxidase inhibitors (MAOIs) and unable to undergo 3-week washout; patients also may not take MAOIs for 2 weeks after completing the study
  • In treatment with (a) depot antipsychotic within 2 weeks of the screening visit
  • Untreated or incompletely treated hypothyroidism
  • Active, unstable medical condition that requires active medication adjustment or surgery
  • Need for electroconvulsive treatment (ECT)
  • Significant risk for harm to themselves or others as a result of randomization to placebo
  • History of malignant neoplasm during the last 5 years

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • University of Iowa College of Medicine

    Iowa City, Iowa, 52242

  • WLA VA Medical Center/UCLA, Psychiatry

    Los Angeles, California, 90073

  • Mount Sinai School of Medicine, Alzheimer's Disease Research Center

    New York, New York, 10029

  • New York State Psychiatric Institute, Columbia University

    New York, New York, 10032

  • Medical University of South Carolina

    North Charleston, South Carolina, 29406

  • Research Center for Clinical Studies, Inc.

    Norwalk, Connecticut, 06851

  • Tuscaloosa VA Medical Center, Department of Psychiatry

    Tuscaloosa, Alabama, 35404

Other trials in United States

About this study

In patients with Alzheimer's disease (AD) who respond to antipsychotic treatment of psychosis and/or agitation/aggression, the relapse risk after discontinuation is not established. AD patients with psychosis and/or agitation/aggression receive 16 weeks of open risperidone treatment (Phase A). Responders are then randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks, (2) risperidone for 16 weeks followed by placebo for 16 weeks, (3) placebo for 32 weeks. The primary outcome is time to relapse of psychosis/agitation.

Read the detailed description

This multicenter study (6 academic sites and 2 non-academic sites) involves treating AD patients (assisted living or nursing home patients, and outpatients) using an atypical antipsychotic, risperidone. In Phase A, 180 AD patients with psychosis and/or agitation/aggression receive open treatment with risperidone for 16 weeks. Responders are randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for the next 32 weeks, (2) risperidone for the next 16 weeks followed by placebo for 16 weeks, or (3) placebo for the next 32 weeks. The primary hypothesis is that in the first 16 weeks of Phase B, relapse risk will be lower with continuation risperidone (Arms 1 + 2) compared to discontinuation on placebo (Arm 3). The secondary hypothesis is that in the second 16 weeks of Phase B, relapse risk will be lower with continuation risperidone (Arm 1) compared to discontinuation on placebo (Arm 2). For both randomized time periods, the proportions who relapse will be compared for interpretive support. This design provides useful data on the efficacy and side effects of longer term treatment with risperidone, and, in particular, critical information about the time to relapse and likelihood of relapse in patients switched from risperidone to placebo. This information is essential to guide the clinician toward optimal use of such medications in one of the most challenging types of patients: the AD patient with psychosis and/or agitation/aggression. The results of this study will also help to address Federal regulations urging early antipsychotic discontinuation in nursing homes.

Being tested
risperidone
Keywords
Risperidone treatment, psychosis, agitation, aggression,, discontinuation, placebo
Medical subject headings
Alzheimer Disease, Psychotic Disorders, Psychomotor Agitation, Aggression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • risperidoneDrug

    Also called Risperdal

    Risperidone open label flexible dose 0.25 to 3 mg daily for first 16 weeks; dose at 16 weeks then fixed for randomized trial

Study groups in NCT00417482
Study groupRoleWhat they receive
Risperidone-risperidoneOtherRisperidone for 16 weeks followed by risperidone for 16 weeks
Receives: Drug: risperidone
Risperidone-PlaceboOtherRisperidone for 16 weeks followed by placebo for 16 weeks
Receives: Drug: risperidone
Placebo-PlaceboOtherPlacebo for 16 weeks followed by placebo for 16 weeks
Receives: Drug: risperidone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Relapse by Study Week 32

    A relapse occurred in Phase B (post-randomization) if both of the following criteria were met:

    1. Increase in the Neuropsychiatric Inventory (NPI) core score of 30% or more OR a 5-point increase from the baseline NPI score at the end of Phase A
    2. A score of 6 (much worse) or 7 (very much worse) on the Clinical Global Impression-Change (CGI-C) at any visit.

    Measured: 0-16 weeks in Phase B (16-32 weeks in study)

Secondary outcomes (7)

  1. Relapse by Study Week 48

    Same definition and criteria as the primary outcome

    Measured: 16-32 weeks in Phase B (32-48 weeks in study)

  2. Mini Mental State Exam (MMSE)

    The MMSE assesses cognition. Scores range from 0-30, with higher scores indicating better cognition. For each subject, the change in MMSE between week 16 and baseline (randomization) was calculated by subtraction, so that a positive value indicates an increase in MMSE over time.

    Measured: Phase B, weeks 1-16 (study weeks 16-32)

  3. Treatment Emergent Symptoms Scale (TESS)

    The Treatment Emergent Symptom Scale (TESS) assesses 26 somatic symptoms. Total scores range from 0-26, with a score of 0 or 1 for each item. Higher scores indicate more somatic symptoms. For each subject, the change in TESS between week 16 and baseline (randomization) was calculated by subtraction, so that a positive value indicates an increase in TESS over time.

    Measured: Phase B, weeks 1-16 (study weeks 16-32)

  4. Extrapyramidal Signs (EPS)

    Extrapyramidal signs, also known as Parkinsonian signs, refer to signs of tremor, rigidity, and bradykinesia (slowed movement) that are seen in Parkinson's disease. Assessment of extrapyramidal signs (EPS) were made with the use of the Simpson-Angus scale (which ranges from 1-40) with higher scores indicating more extrapyramidal signs. For each subject, the change in EPS between week 16 and baseline (randomization) was calculated by subtraction, so that a positive value indicates an increase in EPS over time.

    Measured: Phase B, weeks 1-16 (study weeks 16-32)

  5. AIMS

    The Abnormal Involuntary Movement Scale (AIMS) assesses signs of tardive dyskinesia, a movement disorder that can occur with prolonged use of antipsychotic medication. The AIMS score ranges from 0 to 35, with higher scores indicating more severe symptoms. For each subject, the change in AIMS score between week 16 and randomization was calculated by subtraction, so that a positive value indicates an increase in AIMS over time.

    Measured: Phase B, weeks 1-16 (study weeks 16-32)

  6. Physical Self-Maintenance Scale (PSMS)

    Physical Self-Maintenance Scale, which ranges from 1 to 30, with higher scores indicating WORSE functioning. For each subject, the change in PSMS between week 16 and randomization was calculated by subtraction, so that a positive value indicates an increase in PSMS (worse functioning) over time.

    Measured: Phase B, weeks 1-16 (study weeks 16-32)

  7. Weight

    For each subject, the change in weight in pounds between week 16 and randomization was calculated by subtraction, so that a positive value indicates an increase in weight over time.

    Measured: Phase B, weeks 1-16 (study weeks 16-32)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jan 2007 (estimated)
  2. Study startAug 2004
  3. Primary completionApr 2011
  4. Study completionApr 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
180 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00417482
Sponsor's protocol ID
#5598R
Other IDs
5R01AG021488
Acronym
ADAD
Status last verified
Mar 2013
First submitted
28 Dec 2006
Last updated
24 Apr 2013
Data monitoring committee
Yes

Publications

  • Devanand DP, Mintzer J, Schultz SK, Andrews HF, Sultzer DL, de la Pena D, Gupta S, Colon S, Schimming C, Pelton GH, Levin B. Relapse risk after discontinuation of risperidone in Alzheimer's disease. N Engl J Med. 2012 Oct 18;367(16):1497-507. doi: 10.1056/NEJMoa1114058.

    PubMed 23075176

  • Patel AN, Lee S, Andrews HF, Pelton GH, Schultz SK, Sultzer DL, Mintzer J, de la Pena D, Gupta S, Colon S, Schimming C, Levin B, Devanand DP. Prediction of Relapse After Discontinuation of Antipsychotic Treatment in Alzheimer's Disease: The Role of Hallucinations. Am J Psychiatry. 2017 Apr 1;174(4):362-369. doi: 10.1176/appi.ajp.2016.16020226. Epub 2016 Nov 18.

    PubMed 27855483

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing risperidone in people with Alzheimer Disease and Psychotic Disorders, run by New York State Psychiatric Institute at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Apr 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Relapse by Study Week 32 (time frame: 0-16 weeks in Phase B (16-32 weeks in study)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00417482, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2013.

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