Objective: To evaluate the efficacy of exogenous melatonin in improving sleep quality in Huntington disease (HD) gene carriers.

Background: Various sleep disorders have been identified in HD. Low melatonin levels might explain disrupted circadian behavior in HD. There is evidence of improvement in sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) in individuals receiving melatonin. This is the first study evaluating the efficacy of melatonin in HD.

Method: Randomized, double-blind, placebo-controlled, crossover, proof of concept study. HD gene carriers with a PSQI ≥5 and stable medications for the past 2 months were recruited from the UTHealth, Houston HDSA Center of Excellence. The PSQI, HD Sleep Questionnaire, Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scale (HADS), Clinical Global Impression (CGI) scale, and UHDRSc were administered. Wilcoxon signed-rank test was used to analyze the data.

Results: We enrolled 15 patients (mean age 47.5 years, 46% female), 73% white, 13% African American, and 13% Hispanic. As expected, both melatonin and placebo groups showed significant differences in the PSQI-6 since they were taking medications for sleep. Interestingly, compared to baseline the melatonin group had significantly improved scores in the HD Sleep Questionnaire, and increased scores in the improvement component of the CGI. No differences were noted in the HADS or ESS.

Conclusion: This pilot study in HD gene carriers demonstrates a potential benefit of melatonin for sleep disturbances. Consistent with previous data in other neurodegenerative diseases, melatonin can positively impact sleep quality. Analysis of other variables including changes in BMI, subcomponents of the UHDRS, and measures of quality of life will be forthcoming. Future studies that use objective assessments such as polysomnogram or actigraphy, a larger sample size, and differentiating between disease stages might provide valuable information regarding the utility of melatonin in HD. This abstract was presented at the American Academy of Neurology Annual Meeting in Boston, April 23rd 2023.

References: 1. Kalliolia E, Silajdžić E, Nambron R, Hill NR, Doshi A, Frost C, Watt H, Hindmarsh P, Björkqvist M, Warner TT. Plasma melatonin is reduced in Huntington’s disease. Mov Disord. 2014 Oct;29(12):1511-5. doi: 10.1002/mds.26003. Epub 2014 Aug 27. PMID: 25164424.
2. Fatemeh G, Sajjad M, Niloufar R, Neda S, Leila S, Khadijeh M. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials. J Neurol. 2022 Jan;269(1):205-216. doi: 10.1007/s00415-020-10381-w. Epub 2021 Jan 8. PMID: 33417003.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/melatonin-for-huntington-disease-hd-gene-carriers-with-hd-related-sleep-disturbance-a-pilot-study/