Efficacy of Oral Mixed Tocotrienols in Diabetic Peripheral Neuropathy: A Randomized Clinical Trial.

Autor:	Hor CP; Department of Medicine, Kepala Batas Hospital, Penang, Malaysia., Fung WY; School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia., Ang HA; Clinical Research Centre, Seberang Jaya Hospital, Penang, Malaysia., Lim SC; School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia., Kam LY; School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia., Sim SW; School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia., Lim LH; School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia., Choon WY; School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia., Wong JW; Attest Research Sdn Bhd, Penang, Malaysia., Ch'ng ASH; Clinical Research Centre, Seberang Jaya Hospital, Penang, Malaysia., Beh KKM; Clinical Research Centre, Seberang Jaya Hospital, Penang, Malaysia., Wee HC; Clinical Research Centre, Penang General Hospital, Penang, Malaysia., Ong LM; Clinical Research Centre, Penang General Hospital, Penang, Malaysia., Khan NAK; School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia., Sulaiman SAS; School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia., Shuaib IL; Oncological and Radiological Sciences Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, Malaysia., Bakar A; Butterworth Health Clinic, Penang, Malaysia., Yusof Y; Bandar Tasek Mutiara Health Clinic, Penang, Malaysia., Yusof YM; Seberang Jaya Health Clinic, Penang, Malaysia., Abu Bakar F; Penaga Health Clinic, Penang, Malaysia., Tang WS; Bayan Baru Health Clinic, Penang, Malaysia., Teh HL; Department of Medicine, Kulim Hospital, Kedah, Malaysia., Wahid NA; Sejahtera Centre, Universiti Sains Malaysia, Penang, Malaysia., Saaidin S; Department of Outpatient Care, Sungai Bakap Hospital, Penang, Malaysia., Idris N; Department of Medicine, Kulim Hospital, Kedah, Malaysia., Yoon CK; Department of Medicine, Penang General Hospital, Penang, Malaysia., Ong HN; Bayan Baru Health Clinic, Penang, Malaysia., Ganapathy JT; Bayan Baru Health Clinic, Penang, Malaysia., Loo CE; Clinical Research Centre, Seberang Jaya Hospital, Penang, Malaysia., Samy MM; Clinical Research Centre, Seberang Jaya Hospital, Penang, Malaysia., Zainal H; Clinical Research Centre, Penang General Hospital, Penang, Malaysia., Dharan SCS; Department of Medicine, Kulim Hospital, Kedah, Malaysia., Ooi BY; Clinical Research Centre, Seberang Jaya Hospital, Penang, Malaysia., Teoh PY; Clinical Research Centre, Seberang Jaya Hospital, Penang, Malaysia., Tye YL; Department of Medicine, Seberang Jaya Hospital, Penang, Malaysia., Yeoh CA; Department of Medicine, Seberang Jaya Hospital, Penang, Malaysia., Low DW; Department of Medicine, Seberang Jaya Hospital, Penang, Malaysia., Looi I; Clinical Research Centre, Seberang Jaya Hospital, Penang, Malaysia., Yuen KH; School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.
Jazyk:	angličtina
Zdroj:	JAMA neurology [JAMA Neurol] 2018 Apr 01; Vol. 75 (4), pp. 444-452.
DOI:	10.1001/jamaneurol.2017.4609
Abstrakt:	Importance: Management of painful diabetic peripheral neuropathy remains challenging. Most therapies provide symptomatic relief with varying degrees of efficacy. Tocotrienols have modulatory effects on the neuropathy pathway and may reduce neuropathic symptoms with their antioxidative and anti-inflammatory activities. Objective: To evaluate the efficacy of oral mixed tocotrienols for patients with diabetic peripheral neuropathy. Design, Setting, and Participants: The Vitamin E in Neuroprotection Study (VENUS) was a parallel, double-blind, placebo-controlled trial that recruited participants from January 30, 2011, to December 7, 2014, with 12 months of follow-up. This trial screened 14 289 patients with diabetes from 6 health clinics and ambulatory care units from 5 public hospitals in Malaysia. A total of 391 patients who reported neuropathic symptoms were further assessed with Total Symptom Score (TSS) and Neuropathy Impairment Score (NIS). Patients 20 years or older with a TSS of 3 or higher and an NIS of 2 or higher were recruited. Interventions: Patients were randomized to receive 200 mg of mixed tocotrienols twice daily or matching placebo for 12 months. Patients with hyperhomocysteinemia (homocysteine level ≥2.03 mg/L) received oral folic acid, 5 mg once daily, and methylcobalamin, 500 μg thrice daily, in both groups. Main Outcomes and Measures: The primary outcome was patient-reported neuropathy TSS (lancinating pain, burning pain, paresthesia, and asleep numbness) changes at 12 months. The secondary outcomes were NIS and sensory nerve conduction test result. Results: Of 391 eligible patients, 300 were recruited (130 [43.3%] male; mean [SD] age, 57.6 [8.9] years; mean [SD] duration of diabetes, 11.4 [7.8] years) and 229 (76.3%) completed the trial. The TSS changes between the tocotrienols and placebo groups at 12 months (-0.30; 95% CI, -1.16 to 0.56; P = .49) were similar. No significant differences in NIS (0.60; 95% CI, -1.37 to 2.65; P = .53) and sensory nerve conduction test assessments were found between both groups. In post hoc subgroup analyses, tocotrienols reduced lancinating pain among patients with hemoglobin A1C levels greater than 8% (P = .03) and normohomocysteinemia (homocysteine level <2.03 mg/L; P = .008) at 1 year. Serious adverse events in both groups were similar, except more infections were observed in the tocotrienols group (6.7% vs 0.7%, P = .04). Results reported were of modified intention-to-treat analyses. Conclusions and Relevance: Supplementation of oral mixed tocotrienols, 400 mg/d for 1 year, did not improve overall neuropathic symptoms. The preliminary observations on lancinating pain among subsets of patients require further exploration. Trial Registration: National Medical Research Registry Identifier: NMRR-10-948-7327 and clinicaltrials.gov Identifier: NCT01973400.
Databáze:	MEDLINE
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