Low Protein Diet in Patients With Collagen VI Related Myopathies (LPD)
|ClinicalTrials.gov Identifier: NCT01438788|
Recruitment Status : Completed
First Posted : September 22, 2011
Last Update Posted : October 31, 2016
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Bethlem Myopathy Ullrich Congenital Muscular Dystrophy||Other: Low protein diet||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||8 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Low Protein Diet to Correct Defective Autophagy in Patients With Collagen VI Related Myopathies|
|Study Start Date :||October 2011|
|Primary Completion Date :||June 2013|
|Study Completion Date :||September 2013|
|Experimental: All patients on a low protein diet||
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.
- Reactivation of autophagy measured as a change in Beclin 1 as a marker of autophagy in muscle biopsy from baseline (Day 1) to Day 365 [ Time Frame: one year ]
- Assess the safety of a LPD in patients with BM/UCMD . Nutritional parameters . Muscle mass . Muscle strength [ Time Frame: one year ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01438788
|Istituto Ortopedico Rizzoli|
|Bologna, Italy, 40136|
|Principal Investigator:||Luciano Merlini, MD||Istituto Ortopedico Rizzoli, Bologna, Italy|