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

This study has been completed.
Sponsor:
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
Saarland University
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
Information provided by (Responsible Party):
Frank Jessen, University Hospital, Bonn
ClinicalTrials.gov Identifier:
NCT01047254
First received: January 11, 2010
Last updated: May 25, 2016
Last verified: May 2016
  Purpose

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.


Condition Intervention Phase
Apathy in Dementia
Drug: Elontril
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by University Hospital, Bonn:

Primary Outcome Measures:
  • Change in Apathy Evaluation Scale (AES) score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • NPI total score;NPI caregivers' distress total score;ADCS-ADL; QoL-AD; RUD;ADAScog;MMSE [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 110
Study Start Date: January 2010
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Bupropion
Buproprion 150-300 mg in a flexible dose
Drug: Elontril
flexible dose of Bupropion 150-300 mg
Placebo Comparator: placebo capsule
Placebo
Drug: placebo

  Eligibility

Ages Eligible for Study:   55 Years to 90 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01047254

Locations
Germany
Department of Psychiatry, University Bonn
Bonn, Germany, 53105
Sponsors and Collaborators
University Hospital, Bonn
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
Saarland University
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
Investigators
Principal Investigator: Frank Jessen, MD University Bonn
  More Information

Responsible Party: Frank Jessen, Prof. Dr., University Hospital, Bonn
ClinicalTrials.gov Identifier: NCT01047254     History of Changes
Other Study ID Numbers: 2007-005352-17 
Study First Received: January 11, 2010
Last Updated: May 25, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Dementia
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Tauopathies
Neurodegenerative Diseases
Bupropion
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on December 07, 2016