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

Sponsor

Charite University, Berlin, Germany (Other)

Overall Status

Completed

CT.gov ID

NCT01914965

Collaborator

University of Ulm (Other), Ruhr University of Bochum (Other), University Hospital Muenster (Other)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Apathy Huntington's Disease	Drug: Bupropion Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, 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

Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

May 1, 2014

Actual Study Completion Date :

May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: 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 Names: 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 Names: control

Arm

Intervention/Treatment

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 Names:

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 Names:

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 Names:

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 Names:

control

Outcome Measures

Primary Outcome Measures

Apathy Evaluation Scale (AES-I) [10 weeks]
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) [10 weeks]
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) [10 weeks]
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) [10 weeks]
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 [10 weeks]
The influence of Bupropion compared to placebo on motor scores in patients with HD after ten weeks of treatment.
Cognitive Symptoms [10 weeks]
The influence of Bupropion compared to placebo on MMSE in patients with HD after ten weeks of treatment.
Psychiatric symptoms [10 weeks]
The influence of Bupropion compared to placebo on UHDRS behavioural assessment in patients with HD after ten weeks of treatment.
Activities of daily living [10 weeks]
The influence of Bupropion compared to placebo on UHDRS Functional Assessment in patients with HD after ten weeks of treatment.
Caregiver's distress [10 weeks]
The influence of Bupropion compared to placebo on the NPI caregiver's distress score.
ventral striatal and ventromedial prefrontal activation [10 weeks]
Change of ventral striatal and ventromedial prefrontal activation in response to a reward paradigm as quantified by fMRI.
Adverse events [10 weeks]
The safety and tolerability of Bupropion will be compared with placebo in patients with HD after ten weeks of treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Verified HD mutation carriers aged 25 to 75 years (inclusive) at first dosing
Apathetic as diagnosed by SCIA-D criteria
Stable concomitant medication (no change of medication during last six weeks prior to inclusion)
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
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:

Pregnant or nursing women
Active suicidality based on the answer "yes" in questions 4 and 5 of the Columbia-Suicide Severity Rating Scale (baseline version)
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
Male not using an acceptable barrier method for contraception and donating sperm from screening up to three months following treatment
Presence or history of any medically not controllable disease (e.g. uncontrolled arterial hypertension or diabetes mellitus)
Presence or history of seizures or diagnosed epilepsy or history of severe head trauma (contusion) or CNS tumor
Clinical significant renal (calculated creatine clearance < 60 ml/min) or hepatic dysfunction
Clinical significant depression defined by the NPI depression score (score ≥4 points) at screening
Schizophreniform psychosis within the last 6 months prior to first dose
History of anorexia or bulimia
Severe cognitive disorders defined as a score < 18 in the Mini- Mental State Examination (MMSE) at screening
Marked chorea (UHDRS 4) of face, BOL, trunk or extremities
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
Known hypersensitivity reaction associated with bupropion, gelatine, lactose or magnesium stearate
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
Acute disease state (e.g. nausea, vomiting, fever, diarrhoea, infection) within 7 days of first dose
Definite or suspected personal history or family history of adverse reactions or hypersensitivity to the trial compounds (or to compounds with a similar structure)
Presence of illicit drug and/or alcohol abuse
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
Subjects who are unlikely to be compliant and attend scheduled clinic visits as required
Placement in an institution due to governmental or judicial authorities

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neurologische Klinik der Ruhr-Universität Bochum	Bochum		Germany	44791
2	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Josef Priller, Prof. Dr. med. Josef Priller, Charite University, Berlin, Germany

ClinicalTrials.gov Identifier:

NCT01914965

Other Study ID Numbers:

HDSY001
2009-013698-16

First Posted:

Aug 2, 2013

Last Update Posted:

Sep 9, 2014

Last Verified:

Sep 1, 2014

Keywords provided by Josef Priller, Prof. Dr. med. Josef Priller, Charite University, Berlin, Germany

Huntington's disease

Apathy

Bupropion

Additional relevant MeSH terms:

Huntington Disease

Bupropion

Study Results

No Results Posted as of Sep 9, 2014