Apathy Cure Through Bupropion in Huntington's Disease

Huntington's Disease Clinical Trial

— Action-HD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01914965
• Other study ID #: HDSY001
• Secondary ID: 2009-013698-16
• Status: Completed
• Phase: Phase 2
• First received: July 31, 2013
• Last updated: September 8, 2014
• Start date: June 2012
• Est. completion date: May 2014

Study information

• Verified date: September 2014
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Apathy
• Huntington Disease
• Huntington's Disease

Intervention

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
• 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

Locations

Country	Name	City	State
Germany	Neurologische Klinik der Ruhr-Universität Bochum	Bochum
Germany	Universitätsklinikum Ulm, Klinik für Neurologie	Ulm

Sponsors (4)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Ruhr University of Bochum, University Hospital Muenster, University of Ulm

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Cognitive Symptoms	The influence of Bupropion compared to placebo on MMSE in patients with HD after ten weeks of treatment.	10 weeks	No
Secondary	Psychiatric symptoms	The influence of Bupropion compared to placebo on UHDRS behavioural assessment in patients with HD after ten weeks of treatment.	10 weeks	No
Secondary	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	No
Secondary	Caregiver's distress	The influence of Bupropion compared to placebo on the NPI caregiver's distress score.	10 weeks	No
Secondary	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	No
Secondary	Adverse events	The safety and tolerability of Bupropion will be compared with placebo in patients with HD after ten weeks of treatment.	10 weeks	Yes