A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease.

OBJECTIVE: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. METHODS: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. RESULTS: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. CONCLUSIONS: These data do not justify use of CoQ as a treatment to slow functional decline in HD. CLINICALTRIALSGOV IDENTIFIER: NCT00608881. CLASSIFICATION OF EVIDENCE: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD.

Black widow spider envenomation, a rare cause of Horner's syndrome.

Horner's syndrome involves a triad of eyelid ptosis, miosis, and facial anhidrosis that results from disruption of the oculosympathetic pathway. Acquired Horner's syndrome is associated with a variety of medical conditions including Pancoast tumor and carotid dissection. We report the unique case of a 47-year-old man presenting with Horner's syndrome 4 weeks after black widow spider envenomation. Workup did not reveal any alternative explanatory etiology. We hypothesize that late sequelae of black widow spider envenomation secondary to autonomic nerve injury or retrograde axonal transport after mechanical inoculation may have led to an acquired defect in the oculosympathetic pathway resulting in a Horner's syndrome. This case introduces a rare cause of Horner's syndrome and highlights the importance of environmental exposures in the evaluation of these patients.

Safety and tolerability of high-dosage coenzyme Q10 in Huntington's disease and healthy subjects.

Coenzyme Q10 (CoQ(10)), a potential neuroprotective compound, was previously investigated at a dosage of 600 mg/day in Huntington's disease (HD) patients and demonstrated a trend toward slowing disease progression. Higher CoQ(10) dosages may prove beneficial. We investigated the tolerability and blood levels associated with 1,200, 2,400, and 3,600 mg/day of CoQ(10) in HD and healthy subjects. Twenty-eight subjects (20 HD, 8 healthy) enrolled in a 20-week open-label trial. Subjects started on 1,200 mg/day of CoQ(10), increasing every 4 weeks by 1,200 mg to a maximum dosage of 3,600 mg/day. Monthly evaluations included review of adverse events and CoQ(10) blood levels. Twenty-three subjects (82%) achieved the target dosage of 3,600 mg/day. Six subjects (2 healthy, 4 HD) withdrew prematurely (gastrointestinal (GI) symptoms in 3, worsening HD in 2, and 1 because of a fall). All three serious adverse events occurred in a single subject, and were deemed unrelated to CoQ(10). The most common adverse events seen were GI symptoms. Mean (± SD) CoQ10 blood levels achieved over the course of the trial were as follows: 1.26 ± 1.27 µg/mL (baseline, n = 28), 5.59 ± 2.24 µg/mL (1,200 mg/day, week 4, n = 26), 6.38 ± 3.25 µg/mL (2,400 mg/day, week 8, n = 25), 7.49 ± 4.09 µg/mL (3,600 mg/day, week 12, n = 23), and 6.78 ± 3.36 µg/mL (3,600 mg/day, week 20, n = 20). CoQ(10) was well tolerated with over 80% of subjects achieving the target dosage. Dosages of 2,400 mg/day may provide the best balance between tolerability and blood level achieved. Further studies examining the efficacy of 2,400 mg/day are planned.