Low Protein Diet in Patients With Collagen VI Related Myo... | NCT01438788

Studies
Low Protein Diet in Patients With Collagen VI Related Myopathies

NCT01438788

Sponsor

Istituto Ortopedico Rizzoli

Status

Completed

Last Update Posted

Oct 31, 2016Estimated

Enrollment

8Actual

Phase

Phase 2

Conditions

Bethlem Myopathy
Ullrich Congenital Muscular Dystrophy

Interventions

Low protein diet

Countries

Italy

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Oct 2016

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Oct 2011

Primary Completion Date

Jun 2013Actual

Completion Date

Sep 2013Actual

First Submitted Date

Sep 21, 2011

First Submission Date that Met QC Criteria

Sep 21, 2011

First Posted Date

Sep 22, 2011Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Oct 28, 2016

Last Update Posted Date

Oct 31, 2016Estimated

Oversight Module

Has Data Monitoring Committee (DMC)

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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.

Detailed Description

Not provided

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 2

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

8Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
All patients on a low protein diet	Experimental		Other: Low protein diet

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Low protein diet	Other	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Secondary Outcomes

Measure	Description	Time Frame
Assess the safety of a LPD in patients with BM/UCMD . Nutritional parameters . Muscle mass . Muscle strength		one year

Other Outcomes

Not provided

Eligibility Module

Eligibility 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.

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Name	Affiliation	Role
Luciano Merlini, MD	Istituto Ortopedico Rizzoli, Bologna, Italy	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Istituto Ortopedico Rizzoli		Bologna		40136	Italy

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
21037586	Background	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.
27656840

ID	Term
C535436	Bethlem myopathy
C537521	Scleroatonic muscular dystrophy

ID	Term
D004035	Diet Therapy
D044623	Nutrition Therapy
D013812	Therapeutics
D004032	Diet
D009747