Low Protein Diet in Patients With Collagen VI Related Myopathies

Phase 2

Completed

• Conditions: Ullrich Congenital Muscular Dystrophy; Bethlem Myopathy
• Interventions: Other: Low protein diet

• Registration Number: NCT01438788
• Lead Sponsor: Istituto Ortopedico Rizzoli

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-09-21
• Study First Submitted QC: 2011-09-21
• Study First Posted: 2011-09-22
• Study Start: 2011-10
• Primary Completion: 2013-06
• Study Completion: 2013-09
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-28
• Last Update Posted: 2016-10-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

• Males or females aged ≥18 years.
• Women of childbearing age must have a negative pregnancy test and must use adequate contraception during the study.
• Clinical and molecular diagnosis of Bethlem myopathy or Ullrich congenital muscular dystrophy.
• No previous treatment with CsA within 6 months prior to the start of the study.
• Willing and able to adhere to the study visit schedule and other protocol requirements.
• Written informed consent signed.

Exclusion Criteria

• Current or history of liver or renal disease.
• Pregnant or breast-feeding women.
• Any serious internal medicine condition interfering with the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
All patients on a low protein diet	Low protein diet	-

Primary Outcome Measures

Name	Time	Method
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	one year

Secondary Outcome Measures

Name	Time	Method
Assess the safety of a LPD in patients with BM/UCMD . Nutritional parameters . Muscle mass . Muscle strength	one year

Trial Locations

Locations (1)

Istituto Ortopedico Rizzoli; 🇮🇹 Bologna, Italy