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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01438788
Recruitment Status : Completed
First Posted : September 22, 2011
Last Update Posted : October 31, 2016
Information provided by (Responsible Party):
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.

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)
Primary Purpose: Treatment
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

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. 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 ]

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

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

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 identifier (NCT number): NCT01438788

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

Publications of Results:
Other Publications:
Responsible Party: Istituto Ortopedico Rizzoli Identifier: NCT01438788     History of Changes
Other Study ID Numbers: IOR-0018156
First Posted: September 22, 2011    Key Record Dates
Last Update Posted: October 31, 2016
Last Verified: October 2016

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

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