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Bupropion for the Treatment of Apathy in Alzheimer's Dementia (APA-AD)

Primary Purpose

Apathy in Dementia

Status

Completed

Phase

Phase 3

Locations

Germany

Study Type

Interventional

Intervention

Elontril

placebo

About this trial

This is an interventional treatment trial for Apathy in Dementia

Eligibility Criteria

55 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Mild to moderate Alzheimer's dementia, male and female (NINCDS/ADRDA criteria)
Presence of clinically relevant apathy defined by the Neuropsychiatric Inventory (NPI) apathy item (score of >/= 4 points) and the Marin/Starkstein criteria for apathy
MMSE: 10-25
Outpatient status, not institutionalized
Presence of reliable caregiver
Stable treatment with antidementia drugs for at least three months prior to entry or no treatment with antidementia drugs

Exclusion Criteria:

Other Dementia (e.g. vascular dementia, Lewy-body dementia, fronto-temporal dementia)
Presence of a clinically relevant depression defined by either the NPI depression item (score >/= 4 points) or DSM-IV criteria for major depressive episode (with depressed mood)
Alcoholism and Benzodiazepine addiction
Current treatment with antipsychotics and antidepressants (including St. John's wart)
Current treatment with dopaminergic agents or Amantadin
Current treatment with benzodiazepines
Current treatment with MAO inhibitor (Bupropion contraindication)
Known sensibility to Bupropion treatment
Severe psychiatric disease (including hospitalization) in the last 6 months, suicide attempt, acute psychotic symptoms
Severe physical illness, that do not allow a participation in a 12-week period of treatment
Medical history with seizures
Medical history with tumors of the central nervous system
Severe craniocerebral injury and medical history with cerebral substance defect
Clinically relevant renal disease, liver insufficiency
Simultaneous treatment, which reduces the seizure threshold (e.g. antipsychotics, antidepressants, antimalarial agents, Tramadol, Theophyllin, systemic steroids in higher dose, Chinolone, sedative antihistamines)
Simultaneous treatment, which is metabolized through Cytochrom P450-Isoenzym 2D6 (e.g. these beta blockers: Metoprolol, Proanolol, Timolol, Carvediol, Nebivolol, Typ-1C-Antiarrhyhtmics for e.g. Propafenon, Flecinid) (except Donepezil and Galantamin)
Simultaneous treatment with drugs, which may interfere with the metabolization of Bupropion (e.g. Carbamazepin, Phenytoin, Valproat, Ritonavir, Lopinavir)
Diabetes mellitus, which is therapeutically poorly regulated and treated by medication
Treatment with stimulants and appetite depressants
Participation in other clinical trials with in the last 3 months
Suicidal tendency
Known lactose intolerance

Sites / Locations

Department of Psychiatry, University Bonn

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Bupropion

placebo capsule

Arm Description

Buproprion 150-300 mg in a flexible dose

Placebo

Outcomes

Primary Outcome Measures

Change in Apathy Evaluation Scale (AES) score

Secondary Outcome Measures

NPI total score;NPI caregivers' distress total score;ADCS-ADL; QoL-AD; RUD;ADAScog;MMSE

Full Information

NCT ID

NCT01047254

First Posted

January 11, 2010

Last Updated

May 8, 2017

Sponsor

University Hospital, Bonn

Collaborators

University of Cologne, Physician of neurology, psychiatry and psychotherapy Horn, MD; Bad Honnef, Charite University, Berlin, Germany, Universität Duisburg-Essen, University of Erlangen-Nürnberg, University of Freiburg, University Medical Center Goettingen, Universität des Saarlandes, Johannes Gutenberg University Mainz, Heidelberg University, Philipps University Marburg Medical Center, Ludwig-Maximilians - University of Munich, University of Rostock, University Hospital Tuebingen, University of Ulm

1. Study Identification

Unique Protocol Identification Number

NCT01047254

Brief Title

Bupropion for the Treatment of Apathy in Alzheimer's Dementia

Acronym

APA-AD

Official Title

A 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Bupropion for the Treatment of Apathy in Alzheimer's Dementia(Apa-AD)

Study Type

Interventional

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Completed

Study Start Date

January 2010 (undefined)

Primary Completion Date

July 2014 (Actual)

Study Completion Date

July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University Hospital, Bonn

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Apathy in dementia prevents successful application of non-pharmacological treatments, accelerates cognitive and functional decline and increases disease-related costs by earlier need for full-time care. Apathy is a distinct entity and occurs independently of other neuropsychiatric syndromes, like depression. Today, there is no high-level evidence for any effective treatment of apathy in AD. In contrast to other neuropsychiatric syndromes in AD, like psychosis and depression, and despite its high prevalence and clinical relevance, apathy has never been the primary outcome in a clinical trial. Basic and clinical research has provided a distinct model of the pathophysiology of apathy with dopamine and norepinephrine as the key neurotransmitter systems involved. The antidepressant Bupropion is a dopamine and norepinephrine reuptake inhibitor. There is evidence from case-series, that Bupropion reduces apathy in patients with organic brain disorders. This study will test the efficacy and safety of Bupropion in the treatment of apathy in AD in a 12-week multicenter doubleblind placebo controlled trial. Secondary endpoints will be quality of life of patients, caregivers' distress, ability of patients to perform activities of daily living,utilization of healthcare resources by patients and by caregivers, and cognitive functions.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Apathy in Dementia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

110 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Bupropion

Arm Type

Active Comparator

Arm Description

Buproprion 150-300 mg in a flexible dose

Arm Title

placebo capsule

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Elontril

Intervention Description

flexible dose of Bupropion 150-300 mg

Intervention Type

Drug

Intervention Name(s)

placebo

Primary Outcome Measure Information:

Title

Change in Apathy Evaluation Scale (AES) score

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

NPI total score;NPI caregivers' distress total score;ADCS-ADL; QoL-AD; RUD;ADAScog;MMSE

Time Frame

12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

55 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Mild to moderate Alzheimer's dementia, male and female (NINCDS/ADRDA criteria) Presence of clinically relevant apathy defined by the Neuropsychiatric Inventory (NPI) apathy item (score of >/= 4 points) and the Marin/Starkstein criteria for apathy MMSE: 10-25 Outpatient status, not institutionalized Presence of reliable caregiver Stable treatment with antidementia drugs for at least three months prior to entry or no treatment with antidementia drugs Exclusion Criteria: Other Dementia (e.g. vascular dementia, Lewy-body dementia, fronto-temporal dementia) Presence of a clinically relevant depression defined by either the NPI depression item (score >/= 4 points) or DSM-IV criteria for major depressive episode (with depressed mood) Alcoholism and Benzodiazepine addiction Current treatment with antipsychotics and antidepressants (including St. John's wart) Current treatment with dopaminergic agents or Amantadin Current treatment with benzodiazepines Current treatment with MAO inhibitor (Bupropion contraindication) Known sensibility to Bupropion treatment Severe psychiatric disease (including hospitalization) in the last 6 months, suicide attempt, acute psychotic symptoms Severe physical illness, that do not allow a participation in a 12-week period of treatment Medical history with seizures Medical history with tumors of the central nervous system Severe craniocerebral injury and medical history with cerebral substance defect Clinically relevant renal disease, liver insufficiency Simultaneous treatment, which reduces the seizure threshold (e.g. antipsychotics, antidepressants, antimalarial agents, Tramadol, Theophyllin, systemic steroids in higher dose, Chinolone, sedative antihistamines) Simultaneous treatment, which is metabolized through Cytochrom P450-Isoenzym 2D6 (e.g. these beta blockers: Metoprolol, Proanolol, Timolol, Carvediol, Nebivolol, Typ-1C-Antiarrhyhtmics for e.g. Propafenon, Flecinid) (except Donepezil and Galantamin) Simultaneous treatment with drugs, which may interfere with the metabolization of Bupropion (e.g. Carbamazepin, Phenytoin, Valproat, Ritonavir, Lopinavir) Diabetes mellitus, which is therapeutically poorly regulated and treated by medication Treatment with stimulants and appetite depressants Participation in other clinical trials with in the last 3 months Suicidal tendency Known lactose intolerance

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Frank Jessen, MD

Organizational Affiliation

University Bonn

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Psychiatry, University Bonn

City

Bonn

ZIP/Postal Code

53105

Country

Germany

12. IPD Sharing Statement

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Bupropion for the Treatment of Apathy in Alzheimer's Dementia

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