Low Protein Diet in Patients With Collagen VI Related Myopathies (LPD)

Istituto Ortopedico Rizzoli

Status and phase

Completed

Phase 2

Conditions

Ullrich Congenital Muscular Dystrophy

Bethlem Myopathy

Treatments

Other: Low protein diet

Study type

Interventional

Funder types

Other

Identifiers

NCT01438788

IOR-0018156

Details and patient eligibility

About

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.

Enrollment

8 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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