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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Istituto Ortopedico Rizzoli
ClinicalTrials.gov Identifier:
NCT01438788
First received: September 21, 2011
Last updated: April 17, 2012
Last verified: January 2012
History of Changes
  Purpose
  • 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:

U.S. FDA Resources

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
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
  Eligibility

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

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

Locations
Italy
Istituto Ortopedico Rizzoli
Bologna, Italy
Sponsors and Collaborators
Istituto Ortopedico Rizzoli
Investigators
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: April 17, 2012
Health Authority: Italy: National Institute of Health

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

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

ClinicalTrials.gov processed this record on June 18, 2013