NCT01438788

Low Protein Diet in Patients With Collagen VI Related Myopathies

Low Protein Diet to Correct Defective Autophagy in Patients With Collagen VI Related Myopathies

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Istituto Ortopedico Rizzoli · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

* This is a 2 stage exploratory study with a 3-month observational phase on the natural course, followed by a 12-month, open-label, non-comparative, single-arm, phase II pilot study on the efficacy, safety and tolerability of a low-protein diet (LPD) in 8 adult patients with Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD). * Objective of this trial is to test the effect of a normocaloric LPD to reactivate autophagy in BM/UCMD patients. The primary end point of the study will be the change in muscle biopsy of Beclin 1, a marker of autophagy, at 1 year of LPD treatment when compared to baseline. * The rationale rests on our discoveries that (i) mitochondrial dysfunction mediated by inappropriate opening of the PTP plays a key role in collagen VI myopathies; (ii) defective autophagy with impaired removal of defective mitochondria amplifies the defect; and (iii) reactivation of autophagy with a low-protein diet or treatment with cyclosporine A, the mitochondrial PTP inhibitor, cured Co6a1-/- mice, hinting at a common target among all beneficial treatments - namely autophagy. * Specific aims of this project are to (i) study the modifications of clinical, nutritional and laboratory parameters in a cohort of patients with BM/UCMD during a 3-month observational period before starting the LPD treatment; (ii) assess the effect of a normocaloric LPD in correcting defective autophagy in muscle of patients; (iii) test if new non-invasive biomarkers of activation of autophagy examined in the blood are mirroring the effect of LPD in the muscle biopsy; (iv) assess the clinical efficacy and safety of the LPD with an innovative combination of complementary measures of the nutritional status in patients. * The anticipated output is defining and validating a therapeutic nutritional approach in autophagy upregulation for BM/UCMD.

Conditions

• Bethlem Myopathy
• Ullrich Congenital Muscular Dystrophy

Interventions

Type	Name	Description
OTHER	Low protein diet	Patients will receive a diet with 0.6-0.8 grams of protein/kilogram body weight/day for one year. Bread, biscuits and pasta will be in part substituted with aproteic food.

Timeline

• Start date: 2011-10-01
• Primary completion: 2013-06-01
• Completion: 2013-09-01
• First posted: 2011-09-22
• Last updated: 2016-10-31

Locations

1 site across 1 country: Italy