Apathy Cure Through Bupropion in Huntington's Disease (Action-HD)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
University of Ulm
Ruhr University of Bochum
University Hospital Muenster
Information provided by (Responsible Party):
Josef Priller, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT01914965
First received: July 31, 2013
Last updated: March 7, 2014
Last verified: March 2014
  Purpose

The influence of bupropion compared to placebo on the change of apathy as quantified by the apathy evaluation scale (AES-I, where I [informant] is a friend or family member familiar with the daily activities of the subject) in patients with HD after ten (10) weeks of treatment.


Condition Intervention Phase
Apathy
Huntington's Disease
Drug: Bupropion
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Prospective Crossover Trial Investigating the Efficacy and Safety of the Treatment With Bupropion in Patients With Apathy in Huntington's Disease

Resource links provided by NLM:


Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:
  • Apathy Evaluation Scale (AES-I) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    The influence of Bupropion compared to placebo on the change of apathy as quantified by the apathy evaluation scale (AES-I, where I [informant] is a friend or family member familiar with the daily activities of the subject) in patients with HD after ten weeks of treatment.


Secondary Outcome Measures:
  • AES-C (clinician) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    The influence of Bupropion compared to placebo on the change of apathy as quantified by the apathy evaluation scale (AES-C, where C [clinician] is the trial investigator) in patients with HD after ten weeks of treatment.

  • AES-S (self) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    The influence of Bupropion compared to placebo on the change of apathy as quantified by the apathy evaluation scale (AES-S, where S [self] is the patient) in patients with HD after ten weeks of treatment.

  • Motor symptoms (UHDRS) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    The influence of Bupropion compared to placebo on the UHDRS motor score in patients with HD after ten weeks of treatment.

  • Quantitative grip force motor assessment [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    The influence of Bupropion compared to placebo on motor scores in patients with HD after ten weeks of treatment.

  • Cognitive Symptoms [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    The influence of Bupropion compared to placebo on MMSE in patients with HD after ten weeks of treatment.

  • Psychiatric symptoms [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    The influence of Bupropion compared to placebo on UHDRS behavioural assessment in patients with HD after ten weeks of treatment.

  • Activities of daily living [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    The influence of Bupropion compared to placebo on UHDRS Functional Assessment in patients with HD after ten weeks of treatment.

  • Caregiver's distress [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    The influence of Bupropion compared to placebo on the NPI caregiver's distress score.

  • ventral striatal and ventromedial prefrontal activation [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    Change of ventral striatal and ventromedial prefrontal activation in response to a reward paradigm as quantified by fMRI.

  • Adverse events [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]
    The safety and tolerability of Bupropion will be compared with placebo in patients with HD after ten weeks of treatment.


Estimated Enrollment: 40
Study Start Date: June 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Bupropion
First treatment group: 150 mg bupropion or placebo once daily for 2 weeks, followed by 300 mg bupropion or placebo once daily for subsequent 8 weeks (until week 10; visit 4) First tapering and washout: 150 mg bupropion or placebo once daily for 7 days followed by a washout phase of 1 week on placebo
Drug: Bupropion
Crossover design: Oral administration of 150 mg bupropion once daily for 2 weeks, followed by 300 mg bupropion once daily for subsequent 8 weeks, tapering: 150 mg bupropion once daily for 7 days
Other Name: Wellbutrin, Budeprion, Prexaton, Elontril, Aplenzin
Drug: Placebo
Crossover design: Oral administration of placebo once daily for 2 weeks, followed by placebo once daily for subsequent 8 weeks, tapering: placebo once daily for 7 days
Other Name: control
Placebo Comparator: Placebo
Second treatment group (crossover): placebo or 150 mg bupropion once daily for 2 weeks, followed by placebo or 300 mg bupropion once daily for subsequent 8 weeks (until week 22; visit 6) Second tapering placebo or 150 mg bupropion once daily for 7 days
Drug: Bupropion
Crossover design: Oral administration of 150 mg bupropion once daily for 2 weeks, followed by 300 mg bupropion once daily for subsequent 8 weeks, tapering: 150 mg bupropion once daily for 7 days
Other Name: Wellbutrin, Budeprion, Prexaton, Elontril, Aplenzin
Drug: Placebo
Crossover design: Oral administration of placebo once daily for 2 weeks, followed by placebo once daily for subsequent 8 weeks, tapering: placebo once daily for 7 days
Other Name: control

Detailed Description:

The safety and tolerability of Bupropion in HD.

The influence of Bupropion compared to placebo on the:

  • change of apathy as quantified by the AES-C (clinician) or the AES-S (self),
  • change of motor symptoms (UHDRS) and quantitative grip force motor assessment,
  • change of cognitive symptoms (UHDRS and MMSE),
  • change of psychiatric symptoms (UHDRS, HADS),
  • change of activities of daily living (UHDRS),
  • change of the NPI caregivers' distress score (NPI-D),
  • change of ventral striatal and ventromedial prefrontal activation in response to a reward paradigm as quantified by fMRI.
  Eligibility

Ages Eligible for Study:   25 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Verified HD mutation carriers aged 25 to 75 years (inclusive) at first dosing
  2. Apathetic as diagnosed by SCIA-D criteria
  3. Stable concomitant medication (no change of medication during last six weeks prior to inclusion)
  4. Written informed consent by prospective study participant before conduct of any trial-related procedure. Participant must be able to make an informed decision of whether or not to participate in the study
  5. Patient has a caregiver (family member or friend), who is living in a close relationship with the patient and is willing to give written informed consent (caregiver) before performance of any trial-related procedure

Exclusion criteria:

  1. Pregnant or nursing women
  2. Active suicidality based on the answer "yes" in questions 4 and 5 of the Columbia-Suicide Severity Rating Scale (baseline version)
  3. Woman of childbearing potential, not using highly effective methods of contraception defined as methods with a Pearl Index < 1 such as oral, topical or injected contraception, IUD, contraceptive vaginal ring, or double barrier method such as diaphragm and condom with spermicide) or not surgically sterile (via hysterectomy, ovariectomy or bilateral tubal ligation) or not at least one year post-menopausal
  4. Male not using an acceptable barrier method for contraception and donating sperm from screening up to three months following treatment
  5. Presence or history of any medically not controllable disease (e.g. uncontrolled arterial hypertension or diabetes mellitus)
  6. Presence or history of seizures or diagnosed epilepsy or history of severe head trauma (contusion) or CNS tumor
  7. Clinical significant renal (calculated creatine clearance < 60 ml/min) or hepatic dysfunction
  8. Clinical significant depression defined by the NPI depression score (score ≥4 points) at screening
  9. Schizophreniform psychosis within the last 6 months prior to first dose
  10. History of anorexia or bulimia
  11. Severe cognitive disorders defined as a score < 18 in the Mini- Mental State Examination (MMSE) at screening
  12. Marked chorea (UHDRS 4) of face, BOL, trunk or extremities
  13. Treatment with neuroleptics other than tiapride, MAO-B inhibitors, amantadine, levodopa, D- or D,L-amphetamine or psychostimulants like methylphenidate, modafinil or atomoxetine within 1 month prior to first dose
  14. Known hypersensitivity reaction associated with bupropion, gelatine, lactose or magnesium stearate
  15. Clinically relevant abnormal findings in the ECG, the vitals, in the physical examination or laboratory values at screening that could interfere with the objectives of the study or the safety of the subject as judged by the investigator
  16. Acute disease state (e.g. nausea, vomiting, fever, diarrhoea, infection) within 7 days of first dose
  17. Definite or suspected personal history or family history of adverse reactions or hypersensitivity to the trial compounds (or to compounds with a similar structure)
  18. Presence of illicit drug and/or alcohol abuse
  19. Participation in another investigative drug trial within 2 months or donation of blood within 12 weeks prior to the first dose or during the trial
  20. Subjects who are unlikely to be compliant and attend scheduled clinic visits as required
  21. Placement in an institution due to governmental or judicial authorities
  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: NCT01914965

Locations
Germany
Neurologische Klinik der Ruhr-Universität Bochum
Bochum, Germany, 44791
Universitätsklinikum Münster, Klinik für Neurologie
Münster, Germany, 48149
Universitätsklinikum Ulm, Klinik für Neurologie
Ulm, Germany, 89081
Sponsors and Collaborators
Charite University, Berlin, Germany
University of Ulm
Ruhr University of Bochum
University Hospital Muenster
Investigators
Principal Investigator: Josef Priller, MD Charite University, Berlin, Germany
  More Information

No publications provided

Responsible Party: Josef Priller, Prof. Dr. med. Josef Priller, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT01914965     History of Changes
Other Study ID Numbers: HDSY001, 2009-013698-16
Study First Received: July 31, 2013
Last Updated: March 7, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:
Huntington's disease
Apathy
Bupropion

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Bupropion
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014