Bethlem Myopathy Clinical Trial
— LPDOfficial title:
Low Protein Diet to Correct Defective Autophagy in Patients With Collagen VI Related Myopathies
Verified date | October 2016 |
Source | Istituto Ortopedico Rizzoli |
Contact | n/a |
Is FDA regulated | No |
Health authority | Italy: National Institute of Health |
Study type | Interventional |
- 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.
Status | Completed |
Enrollment | 8 |
Est. completion date | September 2013 |
Est. primary completion date | June 2013 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
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. |
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Italy | Istituto Ortopedico Rizzoli | Bologna |
Lead Sponsor | Collaborator |
---|---|
Istituto Ortopedico Rizzoli |
Italy,
Castagnaro S, Pellegrini C, Pellegrini M, Chrisam M, Sabatelli P, Toni S, Grumati P, Ripamonti C, Pratelli L, Maraldi NM, Cocchi D, Righi V, Faldini C, Sandri M, Bonaldo P, Merlini L. Autophagy activation in COL6 myopathic patients by a low-protein-diet p — View Citation
Grumati P, Coletto L, Sabatelli P, Cescon M, Angelin A, Bertaggia E, Blaauw B, Urciuolo A, Tiepolo T, Merlini L, Maraldi NM, Bernardi P, Sandri M, Bonaldo P. Autophagy is defective in collagen VI muscular dystrophies, and its reactivation rescues myofiber degeneration. Nat Med. 2010 Nov;16(11):1313-20. doi: 10.1038/nm.2247. Epub 2010 Oct 31. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | No | |
Secondary | Assess the safety of a LPD in patients with BM/UCMD . Nutritional parameters . Muscle mass . Muscle strength | one year | Yes |
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