Low Protein Diet in Patients With Collagen VI Related Myopathies (LPD)
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|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|
|Actual Primary Completion Date :||June 2013|
|Actual 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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|