Apathy, Huntington's Disease
Conditions
Keywords
Huntington's disease, Apathy, Bupropion
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.
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.
Interventions
DRUGBupropion
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
DRUGPlacebo
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
Sponsors
University of Ulm
Ruhr University of Bochum
University Hospital Muenster
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
25 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| Psychiatric symptoms | 10 weeks | The influence of Bupropion compared to placebo on UHDRS behavioural assessment in patients with HD after ten weeks of treatment. |
Countries
Germany
Outcome results
None listed