Trial document




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  DRKS00000103

Trial Description

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Title

A 12-week, multicenter, randomized, double-blind, placebo-controlled trial of Bupropion for the treatment of apathy in Alzheimer's Dementia

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Trial Acronym

Apa-AD

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URL of the Trial

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Brief Summary in Lay Language

12-week, multicenter, randomized, doubleblind, placebo-controlled trial to test the efficacy of Bupropion in the treatment of apathy in patients with mild to moderate Alzheimer's Dementia

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Brief Summary in Scientific Language

Apathy is the most common neuropsychiatric disturbance in Alzheimer's Dementia (AD). It is defined by loss of motivation, diminished social interaction and reduced emotional responsiveness. It disrupts communication and interpersonal relationships, thereby creating severe distress for patients, family members and informal caregivers. Apathy 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 pathopysiology 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 heathcare resources by patients and by caregivers, and cognitive functions. In case of a positive outcome, this study would provide first high-level evidence for effective treatment of the most common and distressing neuropsychiatric disturbance in AD.

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Organizational Data

  •   DRKS00000103
  •   2010/01/22
  •   2010/01/11
  •   yes
  •   Approved
  •   155/09, Ethik-Kommission der Medizinischen Fakultät der Rheinischen Friedrich-Wilhelms-Universität Bonn
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Secondary IDs

  •   U1111-1113-2617 
  •   2007-005352-17 
  •   NCT01047254  (ClinicalTrials.gov)
  •   4035568 
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Health Condition or Problem studied

  •   F00 -  Dementia in Alzheimer's disease
  •   R45.3 -  Demoralization and apathy
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Interventions/Observational Groups

  •   Buproprion 150-300mg
  •   Placebo
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist
  •   Placebo
  •   Treatment
  •   Parallel
  •   III
  •   [---]*
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Primary Outcome

Change in Apathy Evaluation Scale (AES) score 12 weeks after randomization

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Secondary Outcome

(1) Change in Neuropsychiatric Inventory (NPI) total score;
(2) Change in the NPI caregivers' distress total score;
(3) Change in the AD Cooperative Study Activities of Daily Living Scale (ADCS-ADL score);
(4) Change in the Quality of Life-AD scale (QoL-AD);
(5) Change in the Resources Utilization in Dementia Questionaire (RUD);
(6) Change in Alzheimer's Disease Assessment Scale, cognitive part (ADAScog score);
(7) Change in Mini-Mental Status Examination (MMSE) score

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • Doctor's Practice 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2010/07/06
  •   216
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   55   Years
  •   90   Years
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Additional 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
Age: 55-90
Outpatient status, not institutionalized
Presence of reliable caregiver
Stable treatment with antidementia drugs for at least three month

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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



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Addresses

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    • Rheinische Friedrich-Wilhelms-Universität Bonn
    • Regina-Pacis-Weg 3
    • 53012  Bonn
    • Germany
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    • Klinik für Psychiatrie und Psychotherapie
    • Mr.  Prof. Dr. med.  Frank  Jessen 
    • Sigmund-Freud-Strasse 25
    • 53105  Bonn
    • Germany
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    • Klinisches Behandlungs- und Forschungszentrum für neurodegenerative Erkrankungen (KBFZ) Klinik für Psychiatrie und Psychotherapie
    • Ms.  Dr. med.  Annika  Spottke 
    • Sigmund-Freud-Strasse 25
    • 53105  Bonn
    • Germany
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Sources of Monetary or Material Support

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    • Projektträger im Deutschen Zentrum für Luft- und Raumfahrt e.v. Gesundheitsforschung
    • Mr.  Dr.  Alexander  Grundmann 
    • Heinrich-Konen-Strasse 1
    • 53175  Bonn
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2014/07/22
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Trial Publications, Results and other Documents

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