ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 4 of 4 for:    "Dysferlinopathy"

Proteasomal Inhibition for Patients With Mis-sense Mutated Dysferlin (Dysferlin)

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.
ClinicalTrials.gov Identifier: NCT01863004
Recruitment Status : Terminated (insufficient enrollment rate)
First Posted : May 27, 2013
Last Update Posted : September 21, 2017
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Brief Summary:
Dysferlin is a protein with an important role in the repair of muscle surface membranes. Mutations in dysferlin cause different forms of muscular dystrophies. Dysferlinopathies are inherited in an autosomal recessive manner, and many patients with this disease harbor mis-sense mutations in at least one of their two pathogenic DYSF alleles. These patients have significantly reduced or absent dysferlin levels in skeletal muscle, suggesting that dysferlin encoded by mis-sense alleles is rapidly degraded by the cell's quality-control system. In a series of in-vitro experiments we showed that mis-sense mutated dysferlin can be salvaged from degradation by proteasomal inhibition. This resulted in an increase of functional dysferlin protein and a subsequent repair of plasma membranes of cultured patient-derived muscle cells. In this proof-of-concept study we would like to test wether proteasomal inhibition can salvage mis-sense mutated dysferlin in patients harboring certain dysferlin mis-sense mutations.

Condition or disease Intervention/treatment Phase
Dysferlinopathy Drug: Bortezomib Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Proteasomal Inhibition for Patients With Mis-sense Mutated Dysferlin
Study Start Date : December 2012
Actual Primary Completion Date : September 15, 2017
Actual Study Completion Date : September 15, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Bortezomib

Arm Intervention/treatment
Experimental: Bortezomib (Velcade®)

This study tests whether salvage of mis-sense mutated dysferlin through proteasomal inhibition seen in cultured muscle cells can be translated into patients harboring dysferlin mis-sense mutations. The proteasomal inhibitor Bortezomib (Velcade®) is already approved as a medication for the treatment of multiple myeloma in Switzerland and in other countries.

Following an administration of a single dose of Bortezomib repeated needle muscle biopsies and blood draws will be performed to assess dysferlin levels in skeletal muscle and blood monocytes over a five day period.

Drug: Bortezomib
Other Name: Velcade®




Primary Outcome Measures :
  1. Dysferlin protein expression levels change from baseline over 5 days assessed by repeated biopsies and blood draws in skeletal muscle and in blood monocytes following administration of a single dose of Bortezomib. [ Time Frame: repeated needle muscle biopsies over a five day period ]
    Repeated needle muscle biopsies and blood draws will be performed after administration of a single dose of Bortezomib (Velcade) to assess dysferlin protein expression in skeletal muscle and in blood monocytes over a five day period.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • must carry at least one allele of a salvageable mis-sense mutation of dysferlin
  • Age ≥ 18 years
  • Written informed consent

Exclusion Criteria:

  • Bleeding disorder
  • Acute or chronic kidney failure (CCL <50 ml/min)
  • Advanced liver disease or active hepatitis
  • Congestive heart failure NYHA III and IV
  • Pregnancy or nursing
  • Immunosuppression (prednisolone doses below 20 mg/d are allowed)
  • Therapy with strong inhibitors of cytochrome P450 3A4
  • HCV or HIV infection
  • Regular alcohol consumption (>14 drinks a week)
  • Drug addiction

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 ClinicalTrials.gov identifier (NCT number): NCT01863004


Locations
Switzerland
Neuromuskuläres Zentrum, Universitätsspital Basel
Basel, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Michael Sinnreich, Prof. Dr. MD Sponsor-Investigator, Neuromuscular Center, Neurology Clinic, University Hospital Basel, Switzerland

Publications of Results:
Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT01863004     History of Changes
Other Study ID Numbers: DYSF001A1
2011DR1148 ( Registry Identifier: Swissmedic Referenznummer 2011DR1148 )
First Posted: May 27, 2013    Key Record Dates
Last Update Posted: September 21, 2017
Last Verified: September 2017

Additional relevant MeSH terms:
Bortezomib
Antineoplastic Agents