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A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia.

ABSTRACT: Previous preclinical studies and a phase I clinical trial suggested that myo-inositol may be a safe and effective lung cancer chemopreventive agent. We conducted a randomized, double blind, placebo-controlled phase IIb study to determine the chemopreventive effects of myo-inositol in smokers with bronchial dysplasia. Smokers with ?1 site of dysplasia identified by autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive oral placebo or myo-inositol, 9 g once a day for 2 weeks, and then twice a day for 6 months. The primary endpoint was change in dysplasia rate after 6 months of intervention on a per-participant basis. Other trial endpoints reported herein include Ki-67 labeling index, blood and bronchoalveolar lavage fluid (BAL) levels of proinflammatory, oxidant/antioxidant biomarkers, and an airway epithelial gene expression signature for PI3K activity. Seventy-four (n = 38 myo-inositol and n = 36 placebo) participants with a baseline and 6-month bronchoscopy were included in all efficacy analyses. The complete response and the progressive disease rates were 26.3% versus 13.9% and 47.4% versus 33.3%, respectively, in the myo-inositol and placebo arms (P = 0.76). Compared with placebo, myo-inositol intervention significantly reduced IL6 levels in BAL over 6 months (P = 0.03). Among those with a complete response in the myo-inositol arm, there was a significant decrease in a gene expression signature reflective of PI3K activation within the cytologically normal bronchial airway epithelium (P = 0.002). The heterogeneous response to myo-inositol suggests a targeted therapy approach based on molecular alterations is needed in future clinical trials to determine the efficacy of myo-inositol as a chemopreventive agent. Cancer Prev Res; 9(12); 906-14. ©2016 AACR.

SUBMITTER: Lam S

PROVIDER: S-EPMC5136333 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia.

Lam Stephen S Mandrekar Sumithra J SJ Gesthalter Yaron Y Allen Ziegler Katie L KL Seisler Drew K DK Midthun David E DE Mao Jenny T JT Aubry Marie Christine MC McWilliams Annette A Sin Don D DD Shaipanich Tawimas T Liu Gang G Johnson Evan E Bild Andrea A Lenburg Marc E ME Ionescu Diana N DN Mayo John J Yi Joanne Eunhee JE Tazelaar Henry H Harmsen William S WS Smith Judith J Spira Avrum E AE Beane Jennifer J Limburg Paul J PJ Szabo Eva E

Cancer prevention research (Philadelphia, Pa.) 20160922 12

Previous preclinical studies and a phase I clinical trial suggested that myo-inositol may be a safe and effective lung cancer chemopreventive agent. We conducted a randomized, double blind, placebo-controlled phase IIb study to determine the chemopreventive effects of myo-inositol in smokers with bronchial dysplasia. Smokers with ≥1 site of dysplasia identified by autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive oral placebo or myo-inositol, 9 g once a day for 2 we ...[more]

PMID: 27658890

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Project description:ObjectiveTo determine the safety and efficacy of orally delivered 4-aminopyridine (4-AP) in persons with Guillain-Barré Syndrome (GBS) >6 months from initial diagnosis.DesignA randomized, double-blind, placebo-controlled, crossover study.SettingTertiary care clinical outpatient program.ParticipantsNineteen participants enrolled (14 male, 5 female; N=19), neurologic impairment secondary to GBS and functional loss on the FIM motor score (stable for ≥12mo) and >3.0 but <5.0 on the American Spinal Injury motor scale. Twelve participants (mean age, 59y; range, 23-77y) completed the study.InterventionsA 4-AP dose-escalation study with 8 weeks in each period with a 3-week washout period, followed by 3 months open-label follow-up.Main outcome measuresFIM motor score was the primary outcome measure; also evaluated were the American Spinal Injury motor strength score (all limbs), handheld dynamometer, 6-minute walk test, Medical Outcomes Study 12-Item Short Form, Center for Epidemiological Studies Depression scale, Positive and Negative Affect Schedule, pain, GBS disability scale, Jepsen-Taylor Hand Function Test, Minnesota Manual Dexterity Test and Minnesota Rate of Manipulation Test, Get Up and Go Test, McGill Pain Inventory, Craig Handicap Assessment and Reporting Technique, and participant self-evaluation.ResultsSeven participants discontinued the study prematurely: 3 because of adverse events, 3 because of travel difficulties or relocation, and 1 because of pretreatment laboratory abnormalities. After removing 3 participants with maximum FIM scores, 4-AP arm trended superior to placebo (P=.065). Patients subjectively could always tell when they were on the active agent usually by tingling sensations or a sense of wellness. No statistically significant differences were found for other outcome measures although there were strong trends.ConclusionsThis study demonstrates the safety of 4-AP in the patient population with GBS as the predominate goal of the study. A trend toward improved function after treatment was noted with most patients electing to stay on the medication after the trial.

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A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia.

Publications

A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia.

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