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

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

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.

Study Overview

• Status: Completed
• Conditions: Huntington's Disease; Apathy
• Intervention / Treatment: Drug: Bupropion; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bochum, Germany, 44791
    • Neurologische Klinik der Ruhr-Universität Bochum
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm, Klinik für Neurologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apathy Evaluation Scale (AES-I)	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.	10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AES-C (clinician)	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.	10 weeks
AES-S (self)	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.	10 weeks
Motor symptoms (UHDRS)	The influence of Bupropion compared to placebo on the UHDRS motor score in patients with HD after ten weeks of treatment.	10 weeks
Quantitative grip force motor assessment	The influence of Bupropion compared to placebo on motor scores in patients with HD after ten weeks of treatment.	10 weeks
Cognitive Symptoms	The influence of Bupropion compared to placebo on MMSE in patients with HD after ten weeks of treatment.	10 weeks
Psychiatric symptoms	The influence of Bupropion compared to placebo on UHDRS behavioural assessment in patients with HD after ten weeks of treatment.	10 weeks
Activities of daily living	The influence of Bupropion compared to placebo on UHDRS Functional Assessment in patients with HD after ten weeks of treatment.	10 weeks
Caregiver's distress	The influence of Bupropion compared to placebo on the NPI caregiver's distress score.	10 weeks
ventral striatal and ventromedial prefrontal activation	Change of ventral striatal and ventromedial prefrontal activation in response to a reward paradigm as quantified by fMRI.	10 weeks
Adverse events	The safety and tolerability of Bupropion will be compared with placebo in patients with HD after ten weeks of treatment.	10 weeks

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: University Hospital Muenster; Ruhr University of Bochum; University of Ulm
• Investigators: Principal Investigator: Josef Priller, MD, Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: July 31, 2013
• First Submitted That Met QC Criteria: July 31, 2013
• First Posted (Estimate): August 2, 2013

Study Record Updates

• Last Update Posted (Estimate): September 9, 2014
• Last Update Submitted That Met QC Criteria: September 8, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Bupropion; Apathy; Huntington's disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Dopamine Uptake Inhibitors; Bupropion
• Other Study ID Numbers: HDSY001; 2009-013698-16 (EudraCT Number)