Dementia of Alzheimer TypePhase 3NCT00190021
Donepezil Treatment of Psychotic Symptoms in Dementia Patients
A Phase 3 study testing donepezil in people with Dementia of Alzheimer Type, run by Beersheva Mental Health Center at 1 site in Israel.
Trial summary
Conventional psychotropic medications may be used to treat behavioral disturbances and psychotic symptoms in patients with dementia and they are the drugs of choice for treating delusions and hallucinations. However the sensitivity to side effects in these patients often restricts the use of these agents (2, 3). Read more about this study
- Who is it for?
- Ages 65 to 90 years
- Conditions the study is for
- Dementia of Alzheimer Type
- What is being tested?
- donepezil
- How many people
- 80 participants
- Where
- 1 siteIsrael
- Study dates
- Start not givento not given
- Phase
- Phase 3
- 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 65 to 90 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- age: 65-90
- DSM-IV diagnosis of Alzheimer's type dementia
- inclusion of psychotic symptoms such as: hallucinations and delusions, aggression/agitation, irritability and disinhibition calling for adminstration of antipsychotic drugs
- duration of psychotic symptoms of at least 2 weeks before start of treatment
- lack of improvement of psychotic symptoms during perphenazine treatment for at least 3 weeks
Who cannot join
- vascular demential
- concurrent Axis I DSM-IV diagnosis (delirium, schizophrenia, delusional disorder and affective disorders)
- significant medical illness (cardiovascular, liver, renal, edocrinal, B12 or folic acid deficience and neurological illnesses)
- drug or alcohol addiction
Trial locations and contacts
1 site in 1 country.
Israel1 site
Beersheva Mental Health Center
Beersheva
Vladimr Lerner, MD, PhD, 9728-6401408, lernervld@yahoo.com
Tzvi Dwolatzky, MD, 9728-6401416, tzvidov@bgu.ac.il
About this study
Official title: Donepezil as Add-On Treatment of Psychotic Symptoms in Patients With Dementia of the Alzheimer's Type
Conventional psychotropic medications may be used to treat behavioral disturbances and psychotic symptoms in patients with dementia and they are the drugs of choice for treating delusions and hallucinations. However the sensitivity to side effects in these patients often restricts the use of these agents (2, 3). Although, atypical antipsychotics have some advantages compared with conventional neuroleptics, they also are associated with side effects (5, 6).
Cholinesterase inhibitors (ChEIs) enhance neuronal transmission by increasing the availability of acetylcholine in muscarinic and nicotinic receptors. According to findings of some researchers ChEIs have psychotropic effects and may play an important role in controlling neuropsychiatric and behavioral disturbances in patients with Alzheimer's disease (7-10). These agents may also contribute to the management of other disorders with cholinergic system abnormalities and neuropsychiatric symptoms such as visual hallucinations (11).
Read more
Donepezil is a piperidine-based reversible, noncompetitive ChEI, which is indicated in the management of patients with Alzheimer's disease of mild to moderate severity (12-14). Preliminary observations suggest the possible value of ChEIs in the amelioration of psychotic symptoms in patients with dementia of the Alzheimer's type (DAT), dementia with Lewy bodies and patients suffering from Parkinson's disease (11-18).
The results of our study (18) indicate that the addition of donepezil to perphenazine resulted in qualitatively superior clinical gains compared to higher doses of neuroleptic therapy without donepezil.
The finding of the pilot study although impressive, stem from data regarding a rather small sample. The present (second) phase of the study will include a larger sample of patients. We now intend to examine 80 inpatients, aged 65-90 years old, suffering from DAT.
Read the detailed description
Criteria for inclusion into the study will be: 1) DSM-IV diagnosis of Dementia of the Alzheimer type with psychotic symptoms such as hallucinations and delusions, aggression/agitation, irritability, and disinhibition that called for the administration of antipsychotic drugs; 2) duration of psychotic symptoms at least 2 weeks before beginning of treatment; 3) lack of improvement of psychotic symptoms (less than 25% on Positive and Negative Symptoms Scale (PANSS) during perphenazine treatment (8 mg/day) for at least three weeks; 4) drug regimen for physical disease of all patients was unchanged for at least three months before the study.
Exclusion criteria include: 1) a vascular dementia; 2) concurrent Axis I DSM-IV diagnoses (delirium, schizophrenia, delusional disorders, and affective disorders) 3) significant medical illness (cardiovascular, liver, renal, endocrinal, vitamin B12 or folic acid deficiency, and neurological illnesses); 4) drug or/and alcohol addiction.
The study design will be a double blind group study, lasting for 9 weeks. Complete physical and laboratory examinations will be performed on all inpatients. Subjects will be randomized in a 1:1 fashion to receive treatment with 4 mg of perphenazine or 5 mg of donepezil or placebo in addition to the perphenazine treatment (8 mg/day) that they have received for the past 3 weeks (baseline). According to mental state (improvement less than 20% on PANSS scores), perphenazine dose will be elevated by 4 mg/day to maximum 16 mg/day in the first group, and donepezil dose will be increased by 5 mg/day to maximum 10 mg/day in the second group) and placebo will be elevated up to 2 capsules/day in the third group. All preparations will be administered in identical capsules made by a professional pharmacist, and supplied in individual number-coded packages.
Assessments for psychotic symptoms will be done using PANSS and CGI at baseline and repeated weekly. Assessments for extrapyramidal side effects will be done using AIMS at baseline and repeated every week. In addition, both at the beginning and at the end of the study, all patients will be assessed with MMSE and GDS. Complete blood profiles, and urine analysis will be performed at screening and at week 9.
References
- Evans DA. Estimated prevalence of Alzheimer's disease in the United States. Milbank Q 1990;68:267-89.
- Schneider LS. Pharmacologic management of psychosis in dementia. J Clin Psychiatry 1999;60(Suppl 8):54-60.
- Tariot PN. Treatment of agitation in dementia. J Clin Psychiatry 1999;60(Suppl 8):11-20.
- Levy ML, Cummings JL, Kahn-Rose R. Neuropsychiatric symptoms and cholinergic therapy for Alzheimer's disease. Gerontology 1999;45(Suppl 1):15-22.
- Casey DE. Side effect profiles of new antipsychotic agents. J Clin Psychiatry 1996;57(Suppl 11):40-5.
- Zayas EM, Grossberg GT. The treatment of psychosis in late life. J Clin Psychiatry 1998;59(Suppl 1):5-10.
- Rogers SL, Doody RS, Mohs RC, et al. Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. Arch Intern Med 1998;158(9):1021-31.
- Wengel SP, Roccaforte WH, Burke WJ. Donepezil improves symptoms of delirium in dementia: implications for future research. J Geriatr Psychiatry Neurol 1998;11(3):159-61.
- Mega MS, Masterman DM, O'Connor SM, et al. The spectrum of behavioral responses to cholinesterase inhibitor therapy in Alzheimer disease. Arch Neurol 1999;56:1388-93.
- Burt T. Donepezil and related cholinesterase inhibitors as mood and behavioral controlling agents. Curr Psychiatry Rep 2000;2:473-8.
- Burke WJ, Roccaforte WH, Wengel SP. Treating visual hallucinations with donepezil. Am J Psychiatry 1999;156:1117-8.
- Rogers SL, Friedhoff LT. The efficacy and safety of donepezil in patients with Alzheimer's disease: results of a US Multicentre, Randomized, Double-Blind, Placebo- Controlled Trial. The Donepezil Study Group. Dementia 1996;7(6):293-303.
- Burns A, Rossor M, Hecker J, et al. The effects of donepezil in Alzheimer's disease - results from a multinational trial. Dement Geriatr Cogn Disord 1999;10:237-44.
- Dooley M, Lamb HM. Donepezil: a review of its use in Alzheimer's disease. Drugs Aging 2000;16:199-226.
- Cummings JL, Gorman DG, Shapira J. Physostigmine ameliorates the delusions of Alzheimer's disease. Biol Psychiatry 1993;33:536-41.
- Kaufer DI, Cummings JL, Christine D. Effect of tacrine on behavioral symptoms in Alzheimer's disease: an open-label study. J Geriatr Psychiatry Neurol 1996;9:1-6.
- McKeith I, Del Ser T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet 2000;356(9247):2031-6.
- Bergman J, Lerner V. Successful use of donepezil for the treatment of psychotic symptoms in patients with Parkinson's disease. Clin Neuropharmacol 2002;25:107-10.
- Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-98.
- Reisberg B, Ferris SH, de Leon MJ, et al. Global Deterioration Scale (GDS). Psychopharmacol Bull 1988;24:661-3.
- Pollock BG, Mulsant BH, Rosen J, et al. Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Am J Psychiatry 2002;159:460-5.
- Sweet RA, Pollock BG, Mulsant BH, et al. Pharmacologic profile of perphenazine's metabolites. J Clin Psychopharmacol 2000;20:181-7.
- Kay S, Opler L, Fiszbein A. Positive and Negative Syndrome Scale (PANSS) Manual. North Tonawanda, NY: Multi-Health Systems; 1986.
- Guy W. ECDEU Assessment Manual for Psychopharmacology, revised. Washington, DC: US Department of Health, Education and Welfare; 1976. .
- Conditions
- Dementia of Alzheimer Type
- Being tested
- donepezil
- Keywords
- Alzheimer's type dementia, donepezil, double-blind
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
donepezilDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Possitive and Negative Syndrome Scale
Clinical Global Impression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2005 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dementia of Alzheimer TypeStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beersheva Mental Health Center
- Sponsor type
- Other government
- Investigators
- Valdimir Lerner, MD, PhD, Principal investigator, Ben-Gurion University of the NegevTzvi Dwolatzky, MD, Principal investigator, Ben-Gurion University of the Negev
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00190021
- Sponsor's protocol ID
- BMHC-3495CTIL
- Status last verified
- Oct 2005
- First submitted
- 11 Sep 2005
- Last updated
- 8 Sep 2010
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Donepezil as Add-On Treatment of Psychotic Symptoms in Patients With Dementia of the Alzheimer's Type
- ClinicalTrials.gov ID
- NCT00190021
- Acronym / sponsor ID
- BMHC-3495CTIL
- Conditions
- Dementia of Alzheimer Type
- Keywords
- Alzheimer's type dementia, donepezil, double-blind
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Beersheva Mental Health CenterOther government
- First posted
- 19 Sep 2005 (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.
Conventional psychotropic medications may be used to treat behavioral disturbances and psychotic symptoms in patients with dementia and they are the drugs of choice for treating delusions and hallucinations. However the sensitivity to side effects in these patients often restricts the use of these agents (2, 3). Although, atypical antipsychotics have some advantages compared with conventional neuroleptics, they also are associated with side effects (5, 6).
Cholinesterase inhibitors (ChEIs) enhance neuronal transmission by increasing the availability of acetylcholine in muscarinic and nicotinic receptors. According to findings of some researchers ChEIs have psychotropic effects and may play an important role in controlling neuropsychiatric and behavioral disturbances in patients with Alzheimer's disease (7-10). These agents may also contribute to the management of other disorders with cholinergic system abnormalities and neuropsychiatric symptoms such as visual hallucinations (11).
Donepezil is a piperidine-based reversible, noncompetitive ChEI, which is indicated in the management of patients with Alzheimer's disease of mild to moderate severity (12-14). Preliminary observations suggest the possible value of ChEIs in the amelioration of psychotic symptoms in patients with dementia of the Alzheimer's type (DAT), dementia with Lewy bodies and patients suffering from Parkinson's disease (11-18).
The results of our study (18) indicate that the addition of donepezil to perphenazine resulted in qualitatively superior clinical gains compared to higher doses of neuroleptic therapy without donepezil.
The finding of the pilot study although impressive, stem from data regarding a rather small sample. The present (second) phase of the study will include a larger sample of patients. We now intend to examine 80 inpatients, aged 65-90 years old, suffering from DAT.
Detailed description
Criteria for inclusion into the study will be: 1) DSM-IV diagnosis of Dementia of the Alzheimer type with psychotic symptoms such as hallucinations and delusions, aggression/agitation, irritability, and disinhibition that called for the administration of antipsychotic drugs; 2) duration of psychotic symptoms at least 2 weeks before beginning of treatment; 3) lack of improvement of psychotic symptoms (less than 25% on Positive and Negative Symptoms Scale (PANSS) during perphenazine treatment (8 mg/day) for at least three weeks; 4) drug regimen for physical disease of all patients was unchanged for at least three months before the study.
Exclusion criteria include: 1) a vascular dementia; 2) concurrent Axis I DSM-IV diagnoses (delirium, schizophrenia, delusional disorders, and affective disorders) 3) significant medical illness (cardiovascular, liver, renal, endocrinal, vitamin B12 or folic acid deficiency, and neurological illnesses); 4) drug or/and alcohol addiction.
The study design will be a double blind group study, lasting for 9 weeks. Complete physical and laboratory examinations will be performed on all inpatients. Subjects will be randomized in a 1:1 fashion to receive treatment with 4 mg of perphenazine or 5 mg of donepezil or placebo in addition to the perphenazine treatment (8 mg/day) that they have received for the past 3 weeks (baseline). According to mental state (improvement less than 20% on PANSS scores), perphenazine dose will be elevated by 4 mg/day to maximum 16 mg/day in the first group, and donepezil dose will be increased by 5 mg/day to maximum 10 mg/day in the second group) and placebo will be elevated up to 2 capsules/day in the third group. All preparations will be administered in identical capsules made by a professional pharmacist, and supplied in individual number-coded packages.
Assessments for psychotic symptoms will be done using PANSS and CGI at baseline and repeated weekly. Assessments for extrapyramidal side effects will be done using AIMS at baseline and repeated every week. In addition, both at the beginning and at the end of the study, all patients will be assessed with MMSE and GDS. Complete blood profiles, and urine analysis will be performed at screening and at week 9.
References
- Evans DA. Estimated prevalence of Alzheimer's disease in the United States. Milbank Q 1990;68:267-89.
- Schneider LS. Pharmacologic management of psychosis in dementia. J Clin Psychiatry 1999;60(Suppl 8):54-60.
- Tariot PN. Treatment of agitation in dementia. J Clin Psychiatry 1999;60(Suppl 8):11-20.
- Levy ML, Cummings JL, Kahn-Rose R. Neuropsychiatric symptoms and cholinergic therapy for Alzheimer's disease. Gerontology 1999;45(Suppl 1):15-22.
- Casey DE. Side effect profiles of new antipsychotic agents. J Clin Psychiatry 1996;57(Suppl 11):40-5.
- Zayas EM, Grossberg GT. The treatment of psychosis in late life. J Clin Psychiatry 1998;59(Suppl 1):5-10.
- Rogers SL, Doody RS, Mohs RC, et al. Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. Arch Intern Med 1998;158(9):1021-31.
- Wengel SP, Roccaforte WH, Burke WJ. Donepezil improves symptoms of delirium in dementia: implications for future research. J Geriatr Psychiatry Neurol 1998;11(3):159-61.
- Mega MS, Masterman DM, O'Connor SM, et al. The spectrum of behavioral responses to cholinesterase inhibitor therapy in Alzheimer disease. Arch Neurol 1999;56:1388-93.
- Burt T. Donepezil and related cholinesterase inhibitors as mood and behavioral controlling agents. Curr Psychiatry Rep 2000;2:473-8.
- Burke WJ, Roccaforte WH, Wengel SP. Treating visual hallucinations with donepezil. Am J Psychiatry 1999;156:1117-8.
- Rogers SL, Friedhoff LT. The efficacy and safety of donepezil in patients with Alzheimer's disease: results of a US Multicentre, Randomized, Double-Blind, Placebo- Controlled Trial. The Donepezil Study Group. Dementia 1996;7(6):293-303.
- Burns A, Rossor M, Hecker J, et al. The effects of donepezil in Alzheimer's disease - results from a multinational trial. Dement Geriatr Cogn Disord 1999;10:237-44.
- Dooley M, Lamb HM. Donepezil: a review of its use in Alzheimer's disease. Drugs Aging 2000;16:199-226.
- Cummings JL, Gorman DG, Shapira J. Physostigmine ameliorates the delusions of Alzheimer's disease. Biol Psychiatry 1993;33:536-41.
- Kaufer DI, Cummings JL, Christine D. Effect of tacrine on behavioral symptoms in Alzheimer's disease: an open-label study. J Geriatr Psychiatry Neurol 1996;9:1-6.
- McKeith I, Del Ser T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet 2000;356(9247):2031-6.
- Bergman J, Lerner V. Successful use of donepezil for the treatment of psychotic symptoms in patients with Parkinson's disease. Clin Neuropharmacol 2002;25:107-10.
- Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-98.
- Reisberg B, Ferris SH, de Leon MJ, et al. Global Deterioration Scale (GDS). Psychopharmacol Bull 1988;24:661-3.
- Pollock BG, Mulsant BH, Rosen J, et al. Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Am J Psychiatry 2002;159:460-5.
- Sweet RA, Pollock BG, Mulsant BH, et al. Pharmacologic profile of perphenazine's metabolites. J Clin Psychopharmacol 2000;20:181-7.
- Kay S, Opler L, Fiszbein A. Positive and Negative Syndrome Scale (PANSS) Manual. North Tonawanda, NY: Multi-Health Systems; 1986.
- Guy W. ECDEU Assessment Manual for Psychopharmacology, revised. Washington, DC: US Department of Health, Education and Welfare; 1976. .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 65 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (5 listed)
- age: 65-90
- DSM-IV diagnosis of Alzheimer's type dementia
- inclusion of psychotic symptoms such as: hallucinations and delusions, aggression/agitation, irritability and disinhibition calling for adminstration of antipsychotic drugs
- duration of psychotic symptoms of at least 2 weeks before start of treatment
- lack of improvement of psychotic symptoms during perphenazine treatment for at least 3 weeks
Key exclusion criteria (4 listed)
- vascular demential
- concurrent Axis I DSM-IV diagnosis (delirium, schizophrenia, delusional disorder and affective disorders)
- significant medical illness (cardiovascular, liver, renal, edocrinal, B12 or folic acid deficience and neurological illnesses)
- drug or alcohol addiction
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 |
|---|---|---|
| donepezil | Drug | – |
Primary outcome
Possitive and Negative Syndrome Scale
Clinical Global Impression
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2010.
Related trials for Dementia of Alzheimer Type
RecruitingPhase 2
A Study to Investigate the Safety and Effectiveness of SAR448851 in Participants With Early Alzheimer's Disease
Dementia, Alzheimer's Type, Alzheimer's Disease
Active, not recruiting
Effectiveness of Strength-based Intervention for Elderly With Dementia Living in the Community
Dementia, Mild Cognitive Impairment
RecruitingObservational study
Activation Sarcoma: PROMIS and Mobility Evaluation in Sarcoma Patients
Sarcoma, Giant Cell Tumor of Bone
Enrolling by invitationPhase 2
Tau PET Outcomes With Anti-amyloid Immunotherapies
Cognitive Impairment, Mild, Dementia, Mild
Active, not recruitingPhase 2/3
Effect of 10 mg Xanamem on Dementia Due to Alzheimer's Disease
Dementia Moderate, Dementia, Mild
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.
Valdimir Lerner, MD, PhD principal investigator
Ben-Gurion University of the Negev
Tzvi Dwolatzky, MD principal investigator
Ben-Gurion University of the Negev
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing donepezil in people with Dementia of Alzheimer Type, run by Beersheva Mental Health Center at 1 site in Israel.
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 5 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 8 Sep 2010. 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 Israel. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Vladimir Lerner, MD, PhD (9728-6401408, lernervld@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Possitive and Negative Syndrome Scale. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Sep 2010.