Apathy Cure Through Bupropion 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.

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 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