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Clinical Trial
. 2017 Mar 21;12(3):e0173872.
doi: 10.1371/journal.pone.0173872. eCollection 2017.

Bupropion for the Treatment of Apathy in Huntington's Disease: A Multicenter, Randomised, Double-Blind, Placebo-Controlled, Prospective Crossover Trial

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Free PMC article
Clinical Trial

Bupropion for the Treatment of Apathy in Huntington's Disease: A Multicenter, Randomised, Double-Blind, Placebo-Controlled, Prospective Crossover Trial

Harald Gelderblom et al. PLoS One. .
Free PMC article

Abstract

Objective: To evaluate the efficacy and safety of bupropion in the treatment of apathy in Huntington's disease (HD).

Methods: In this phase 2b multicentre, double-blind, placebo-controlled crossover trial, individuals with HD and clinical signs of apathy according to the Structured Clinical Interview for Apathy-Dementia (SCIA-D), but not depression (n = 40) were randomized to receive either bupropion 150/300mg or placebo daily for 10 weeks. The primary outcome parameter was a significant change of the Apathy Evaluation Scale (AES) score after ten weeks of treatment as judged by an informant (AES-I) living in close proximity with the study participant. The secondary outcome parameters included changes of 1. AES scores determined by the patient (AES-S) or the clinical investigator (AES-C), 2. psychiatric symptoms (NPI, HADS-SIS, UHDRS-Behavior), 3. cognitive performance (SDMT, Stroop, VFT, MMSE), 4. motor symptoms (UHDRS-Motor), 5. activities of daily function (TFC, UHDRS-Function), and 6. caregiver distress (NPI-D). In addition, we investigated the effect of bupropion on brain structure as well as brain responses and functional connectivity during reward processing in a gambling task using magnetic resonance imaging (MRI).

Results: At baseline, there were no significant treatment group differences in the clinical primary and secondary outcome parameters. At endpoint, there was no statistically significant difference between treatment groups for all clinical primary and secondary outcome variables. Study participation, irrespective of the intervention, lessened symptoms of apathy according to the informant and the clinical investigator.

Conclusion: Bupropion does not alleviate apathy in HD. However, study participation/placebo effects were observed, which document the need for carefully controlled trials when investigating therapeutic interventions for the neuropsychiatric symptoms of HD.

Trial registration: ClinicalTrials.gov 01914965.

Conflict of interest statement

Competing Interests: Harald Gelderblom has no competing interests. Torsten Wüstenberg has no competing interests. Tim McLean has no competing interests. Lisanne Mütze has no competing interests. Wilhelm Fischer has no competing interests. Carsten Saft has no competing interests in relation to the submitted trial. Carsten Saft reports grants from Teva Endowed Professorship, grants from 'Cure Huntington's Disease Initiative´ (CHDI), grants from Biogen, personal fees from Temmler Pharma GmbH & Co.KG, personal fees from Desitin, received institutional compensation and/or travel or accommodation payments in the context of the observational studies Registry-Study of the Euro-HD-Network, the ENROLL-HD Study (CHDI), in the context of the MitoNet-study, and in the context of the ACR16-Study (Neurosearch), the AFQ-Study (Novartis), the Selisistat-Studies (Siena Biotech), the PRIDE-HD-Study (TEVA), the Amaryllis-Study (Pfizer) as well as the IONIS Antisense trial (IONIS-HTTRx). He is a member of the EHDN (European Huntington’s Disease Network) "Registry Steering Committee” since 01/2013, since 04/13 a member of the "Stiftungsrates der Huntington-Stiftung" (Research foundation), since 06/13 on steering committee: Deep Brain Stimulation (DBS) of the Globus pallidus (GP) in Huntington’s disease: A prospective, randomizied, controlled multi-centre study, since 09/14 a member of the EHDN "Scientific and Bioethics Advisory Committee (SBAC)”, and a member of the Scientific Committee of the German patient organisation (Deutsche Huntington Hilfe). Rainer Hoffmann has no competing interests. Sigurd Süssmuth has no competing interests. Peter Schlattmann has no competing interests. Erik van Duijn has no competing interests. Bernhard Landwehrmeyer has no competing interests in relation to the submitted trial. He has provided consulting services, advisory board functions, clinical trial services and/or lectures for Affiris, AOP Orphan Pharmaceuticals AG, Desitin, GlaxoSmithKline, Hoffmann-La Roche, Ionis Pharma, Pfizer, Prana Biotechnology, Raptor Pharmaceuticals, and TEVA and has received research grant support from the CHDI Foundation, the Bundesministerium für Bildung und Forschung (BMBF), the Deutsche Forschungsgemeinschaft (DFG), the European Commission (EU-FP7). His study site Ulm has received compensation in the context of the observational REGISTRY-Study of EHDN. Josef Priller is an academic editor of PLOS ONE. He has no competing interests in relation to the submitted trial. He has advisory function for Neurimmune, has a licensed patent with Epomedics, gave paid lectures for Desitin Arzneimittel GmbH and has provided trial services for EHDN, Teva, Pfizer, TauRx, DZNE (Deutsches Zentrum für Neurodegenerative Erkrankungen), CHDI, Axovant. He is a member of DGPPN (Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde), DGBP (Deutsche Gesellschaft für Biologische Psychiatrie), IGSLI (International Group for The Study of Lithium Treated Patients), DZNE and EHDN. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. CONSORT flow diagram.

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Grant support

This work was supported by Huntington Study Group (HSG), Rochester, New York, USA (www.huntingtonstudygroup.org); Huntington Society of Canada (HSC), Ontario, Canada (www.huntingtonsociety.ca); European Huntington’s Disease Network (EHDN), Ulm, Germany (www.euro-hd.net); Cluster of Excellence NeuroCure, Charité – Universitätsmedizin Berlin (www.neurocure.de). EHDN funded data collection but had no role in study design, data analysis, decision to publish, or preparation of the manuscript. HSG, HSC and NeuroCure had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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