Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial.

IMPORTANCE: Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. OBJECTIVE: To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. DESIGN, SETTING, AND PARTICIPANTS: Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. INTERVENTIONS: Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. MAIN OUTCOMES AND MEASURES: Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form- physical functioning subscale score (SF-36), and the change in the Berg Balance Test. RESULTS: Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was -2.5 units (95% CI, -3.7 to -1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, -0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. CONCLUSIONS AND RELEVANCE: Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01795859.

Huntington's Disease and Employment: The Relative Contributions of Cognitive and Motor Decline to the Decision to Leave Work.

BACKGROUND: Huntington's disease (HD) presents with motor, cognitive, and behavioral symptoms that impair functional capacity and the ability to maintain employment. The relative contribution of cognitive decline to work disability remains controversial. OBJECTIVE: To evaluate the association of cognitive decline, compared with motor decline, with the decision to leave work. METHODS: Data from the Enroll-HD observational study were analyzed. The correlation of age of cognitive symptom onset and age of motor symptom onset with age at leaving work was assessed. The association of the Stroop Color Naming Test (SCNT) cognitive assessment and the Total Motor Score (TMS) assessment (reverse scored) with the Total Functional Capacity (TFC) assessment was also assessed. RESULTS: For every year delay in cognitive symptom onset, there was a 0.806 year increase in age at leaving work (SE = 0.030, p < 0.001, adj-R2 = 0.628). For every year delay of motor symptom onset, there was a 0.814 year increase in age at leaving work (SE = 0.031, p < 0.001, adj-R2 = 0.603). For every additional correct SCNT response given and for every unit increase in TMS, there was a 0.105 unit increase (SE = 0.006, p < 0.001, adj-R2 = 0.315) and a 0.104 unit decrease in TFC (SE = 0.003, p < 0.001, adj-R2 = 0.640), respectively. CONCLUSIONS: Cognitive symptoms have a significant association, comparable to that of motor symptoms, with occupational functioning and the decision to leave work, suggesting that development of therapies for both cognitive and motor decline would be important for allowing people with HD to remain in the workforce longer.

Qualitative Evaluation of Medical Information Processing Needs of 60 Women Choosing Ovarian Cancer Surveillance or Prophylactic Oophorectomy.

Thirty women who had prophylactic oophorectomy (PO) and thirty women undergoing ovarian cancer surveillance (OCS) completed a one-time in-depth telephone interview exploring information gathering and decision-making processes. There were close similarities between groups, including age, race, marital status, education, menopausal status, number undergoing genetic testing for BRCA mutations, and number of prophylactic mastectomies. The majority of participants indicated overall satisfaction with their final decision. However, many described the information gathering process as frustrating and anxiety provoking. Participants in both groups expressed a need to process medical information within the context of individual psychosocial needs and personal perceptions and experiences. There were recurrent themes with regard to informational and psychosocial needs and personal perceptions and experiences that impacted decision-making process for these women. The present paper is a companion paper to Swisher et al. (J Repr Med 2001, 46:87-94) with the focus of this paper to illustrate the medical informational processing needs identified by this group of women.