Alzheimer's DiseasePhase 4NCT00009217
Treatment of Behavioral Symptoms in Alzheimer's Disease
A Phase 4 study testing Haloperidol-Haloperidol in people with Alzheimer's Disease and Psychosis, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
The optimal strategy for the treatment of behavioral complications in patients with probable Alzheimer's disease (AD) remains unclear. The objective of this study is to evaluate the risk of relapse following discontinuation of haloperidol in patients with Alzheimer's disease (AD) with psychosis or agitation who… Read more about this study
- Who is it for?
- Ages 50 to 95 years
- Conditions the study is for
- Alzheimer's Disease, Psychosis, Agitation
- What is being tested?
- Haloperidol-Haloperidol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 1999to Dec 2004
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- Meets DSM-IV criteria for dementia either sex, age 50-95 years
- Meets NINCDS-ADRDA criteria for probable Alzheimer's disease
- Meets Folstein Mini-Mental State Exam score of 5-26, inclusive
- Intellectual impairment reported for at least six months
- Availability of family member who has had direct contact with the patient for an average of at least once every week during the three months prior to study entry
- Has current symptoms of psychosis or agitation. Criteria for "psychosis" requires the presence of delusions and/or hallucinations identified by the Columbia University Scale for Psychopathology in Alzheimer's Disease (CUSPAD) and a minimum Brief Psychiatric Rating Scale (BPRS) psychosis factor score of at least 4 (moderate severity) on one of the following two items: These two items comprise the psychosis factor, excluding the item for conceptual disorganization. Agitation is defined as a score of greater than 3 (present at least 10 days per month) on one or more of the CERAD Behavioral Rating Scale for Dementia items for agitation, purposeless wandering, verbal aggression or physical aggression.
- Free of psychotropic medication for at least two weeks prior to study entry, or able to tolerate medication washout for this period.
- Informed consent by patient and family member, as per IRB procedures at New York State Psychiatric Institute.
Who cannot join
- Acute unstable medical condition, delirium, alcohol or substance abuse or dependence within the past 1 year
- Clinical evidence of stroke, other dementias including vascular or Lewy body or frontotemporal dementia, multiple sclerosis, Parkinson's disease, Huntington's disease, tardive dyskinesia
- Diagnosis of a psychotic disorder antedating the onset of dementia
- Antipsychotic medication usage during 4 weeks prior to study entry
- Contraindication to the use of haloperidol
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
The optimal strategy for the treatment of behavioral complications in patients with probable Alzheimer's disease (AD) remains unclear.
The objective of this study is to evaluate the risk of relapse following discontinuation of haloperidol in patients with Alzheimer's disease (AD) with psychosis or agitation who respond to it.
Read more
In Phase A of this study, AD outpatients with behavioral complications receive 20 weeks of open haloperidol treatment with an oral dose of 1-5 mg daily, titrated individually to achieve the optimal trade-off between efficacy and side effects. Responders to Phase A participate in Phase B, a 24-week continuation trial in which patients are randomized to continuation haloperidol or placebo.
The primary outcome is the time to relapse of psychosis or behavioral disturbance.
Read the detailed description
The study involves two phases. Outpatients with AD who meet inclusion/ exclusion criteria enter Phase A, the 20 week open acute treatment phase that uses a flexible dose regimen of haloperidol 1-5 mg daily. Haloperidol is started at an oral dose of 1 mg daily, with subsequent dose titration in 1 mg increments until the optimal dose is reached, i.e., optimal trade-off between efficacy and side effects. At the end of Phase A, patients who do not meet criteria for clinical response exit the protocol and is treated openly with alternative medications.
Phase A responders enter Phase B, a 24-week random assignment, placebo-controlled, continuation trial. Randomization is stratified by the severity of dementia and by the presence of psychosis. Half the patients are randomized to haloperidol (continuing at the same dose as at the end of Phase A), and the other half are randomized to placebo. Patients who relapse during Phase B exit the protocol and receive open treatment.
In Phase A, patients are followed at 0, 2, 4 weeks and every 4 weeks thereafter until 20 weeks. In the discontinuation trial, Phase B, patients are followed at 0, 1, 2, 4, week time points and every 4 weeks thereafter until 24 weeks. If a patient shows signs of relapse, the patient is brought in for more frequent visits, regardless of the stage of the protocol.
- Conditions
- Alzheimer's Disease, Psychosis, Agitation
- Being tested
- Haloperidol-Haloperidol, Haloperidol-Placebo
- Keywords
- Alzheimer's disease, psychosis, agitation, haloperidol
- Medical subject headings
- Alzheimer Disease, Psychotic Disorders, Psychomotor Agitation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Haloperidol-HaloperidolDrug
Also called Haldol
Haloperidol open label flexible dose 1-5 mg daily for 20 weeks followed by haloperidol double-blind 1-5 mg for 24 weeks
Haloperidol-PlaceboDrug
Also called Haldol
Haloperidol open-label flexible dose of 1-5 mg for 20 weeks followed by placebo double-blind for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Haloperidol-Haloperidol | Active comparator | Haloperidol for 20 weeks followed by haloperidol for 24 weeks Receives: Drug: Haloperidol-Haloperidol |
| Haloperidol-Placebo | Placebo comparator | Haloperidol for 20 weeks followed by placebo for 24 weeks Receives: Drug: Haloperidol-Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
For the primary hypothesis, the primary endpoint is time to relapse.
Measured: 0-24 weeks in Phase B
Secondary outcomes (3)
Severity of target symptoms at the end of Phase A as a predictor of relapse
Measured: 0-24 weeks in Phase B
Severity of Brief Psychiatric Rating Scale psychosis and hostile suspiciousness factor scores
Measured: 0-20 weeks in Phase A and 0-24 weeks in Phase B
MMSE and Blessed Functional Activity Scale
Measured: 0-20 weeks in Phase A and 0-24 weeks in Phase B
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2001 (estimated)
- Study startJan 1999
- Primary completionDec 2004
- Study completionDec 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Davangere Devanand, M.D., Principal investigator, Columbia University College of Physicians and Surgeon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00009217
- Sponsor's protocol ID
- #4051R
- Other IDs
- R01MH055735
- Status last verified
- Feb 2012
- First submitted
- 23 Jan 2001
- Last updated
- 24 May 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Devanand DP, Pelton GH, Cunqueiro K, Sackeim HA, Marder K. A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation trial following response to haloperidol treatment of psychosis and agitation in Alzheimer's disease. Int J Geriatr Psychiatry. 2011 Sep;26(9):937-43. doi: 10.1002/gps.2630. Epub 2010 Dec 28.
PubMed 21845596
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Behavioral Symptoms in Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT00009217
- Acronym / sponsor ID
- #4051R
- Conditions
- Alzheimer's Disease, Psychosis, Agitation
- Keywords
- Alzheimer's disease, psychosis, agitation, haloperidol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Jan 1999
- Primary completion
- Dec 2004 (actual)
- Study completion
- Dec 2004 (actual)
- First posted
- 24 Jan 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The optimal strategy for the treatment of behavioral complications in patients with probable Alzheimer's disease (AD) remains unclear.
The objective of this study is to evaluate the risk of relapse following discontinuation of haloperidol in patients with Alzheimer's disease (AD) with psychosis or agitation who respond to it.
In Phase A of this study, AD outpatients with behavioral complications receive 20 weeks of open haloperidol treatment with an oral dose of 1-5 mg daily, titrated individually to achieve the optimal trade-off between efficacy and side effects. Responders to Phase A participate in Phase B, a 24-week continuation trial in which patients are randomized to continuation haloperidol or placebo.
The primary outcome is the time to relapse of psychosis or behavioral disturbance.
Detailed description
The study involves two phases. Outpatients with AD who meet inclusion/ exclusion criteria enter Phase A, the 20 week open acute treatment phase that uses a flexible dose regimen of haloperidol 1-5 mg daily. Haloperidol is started at an oral dose of 1 mg daily, with subsequent dose titration in 1 mg increments until the optimal dose is reached, i.e., optimal trade-off between efficacy and side effects. At the end of Phase A, patients who do not meet criteria for clinical response exit the protocol and is treated openly with alternative medications.
Phase A responders enter Phase B, a 24-week random assignment, placebo-controlled, continuation trial. Randomization is stratified by the severity of dementia and by the presence of psychosis. Half the patients are randomized to haloperidol (continuing at the same dose as at the end of Phase A), and the other half are randomized to placebo. Patients who relapse during Phase B exit the protocol and receive open treatment.
In Phase A, patients are followed at 0, 2, 4 weeks and every 4 weeks thereafter until 20 weeks. In the discontinuation trial, Phase B, patients are followed at 0, 1, 2, 4, week time points and every 4 weeks thereafter until 24 weeks. If a patient shows signs of relapse, the patient is brought in for more frequent visits, regardless of the stage of the protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Haloperidol-Haloperidol | Active comparator | Drug: Haloperidol-HaloperidolHaloperidol for 20 weeks followed by haloperidol for 24 weeks |
| Haloperidol-Placebo | Placebo comparator | Drug: Haloperidol-PlaceboHaloperidol for 20 weeks followed by placebo for 24 weeks |
Who may qualify
- Ages
- 50 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Meets DSM-IV criteria for dementia either sex, age 50-95 years
- Meets NINCDS-ADRDA criteria for probable Alzheimer's disease
- Meets Folstein Mini-Mental State Exam score of 5-26, inclusive
- Intellectual impairment reported for at least six months
- Availability of family member who has had direct contact with the patient for an average of at least once every week during the three months prior to study entry
Key exclusion criteria (5 listed)
- Acute unstable medical condition, delirium, alcohol or substance abuse or dependence within the past 1 year
- Clinical evidence of stroke, other dementias including vascular or Lewy body or frontotemporal dementia, multiple sclerosis, Parkinson's disease, Huntington's disease, tardive dyskinesia
- Diagnosis of a psychotic disorder antedating the onset of dementia
- Antipsychotic medication usage during 4 weeks prior to study entry
- Contraindication to the use of haloperidol
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Haloperidol-HaloperidolAlso: HaldolHaloperidol open label flexible dose 1-5 mg daily for 20 weeks followed by haloperidol double-blind 1-5 mg for 24 weeks | Drug | Haloperidol-Haloperidol |
| Haloperidol-PlaceboAlso: HaldolHaloperidol open-label flexible dose of 1-5 mg for 20 weeks followed by placebo double-blind for 24 weeks | Drug | Haloperidol-Placebo |
Primary outcome
For the primary hypothesis, the primary endpoint is time to relapse.
Time frame: 0-24 weeks in Phase B
3 secondary outcomes
Severity of target symptoms at the end of Phase A as a predictor of relapse
Time frame: 0-24 weeks in Phase B
Severity of Brief Psychiatric Rating Scale psychosis and hostile suspiciousness factor scores
Time frame: 0-20 weeks in Phase A and 0-24 weeks in Phase B
MMSE and Blessed Functional Activity Scale
Time frame: 0-20 weeks in Phase A and 0-24 weeks in Phase B
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2016.
- Results publication: PubMed 21845596Devanand DP, Pelton GH, Cunqueiro K, Sackeim HA, Marder K. A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation trial following response to haloperidol treatment of psychosis and agitation in Alzheimer's disease. Int J Geriatr Psychiatry. 2011 Sep;26(9):937-43. doi: 10.1002/gps.2630. Epub 2010 Dec 28.
- link to Pubmed abstractLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Davangere Devanand, M.D. principal investigator
Columbia University College of Physicians and Surgeon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Haloperidol-Haloperidol in people with Alzheimer's Disease and Psychosis, run by New York State Psychiatric Institute at 1 site 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 8 inclusion and 5 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 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
For the primary hypothesis, the primary endpoint is time to relapse. (time frame: 0-24 weeks in Phase B). 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 NCT00009217, which also lists 1 linked publication.
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 May 2016.