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

This study has been completed.
Information provided by (Responsible Party):
Istituto Ortopedico Rizzoli
ClinicalTrials.gov Identifier:
First received: September 21, 2011
Last updated: November 13, 2013
Last verified: October 2013
  • 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 Intervention Phase
Bethlem Myopathy
Ullrich Congenital Muscular Dystrophy
Other: Low protein diet
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Low Protein Diet to Correct Defective Autophagy in Patients With Collagen VI Related Myopathies

Resource links provided by NLM:

Further study details as provided by Istituto Ortopedico Rizzoli:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess the safety of a LPD in patients with BM/UCMD . Nutritional parameters . Muscle mass . Muscle strength [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Enrollment: 8
Study Start Date: October 2011
Study Completion Date: September 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01438788

Istituto Ortopedico Rizzoli
Bologna, Italy, 40136
Sponsors and Collaborators
Istituto Ortopedico Rizzoli
Principal Investigator: Luciano Merlini, MD Istituto Ortopedico Rizzoli, Bologna, Italy
  More Information

No publications provided

Responsible Party: Istituto Ortopedico Rizzoli
ClinicalTrials.gov Identifier: NCT01438788     History of Changes
Other Study ID Numbers: IOR-0018156
Study First Received: September 21, 2011
Last Updated: November 13, 2013
Health Authority: Italy: National Institute of Health

Keywords provided by Istituto Ortopedico Rizzoli:
Bethlem myopathy
Ullrich congenital muscular dystrophy
Low protein diet
Pilot clinical trial

Additional relevant MeSH terms:
Muscular Diseases
Muscular Disorders, Atrophic
Muscular Dystrophies
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Pathologic Processes
Joint Diseases

ClinicalTrials.gov processed this record on April 17, 2014