Recruiting
Phase 1
Phase 2

Myoblasts

Sponsor:

CHU de Quebec-Universite Laval

Code:

NCT02196467

Conditions

Duchenne Muscular Dystrophy

Eligibility Criteria

Sex: Male

Age: 16+

Healthy Volunteers: Not accepted

Interventions

Myoblast transplantation

Saline injection

Study Details

Brief summary:

This Phase I/II of the clinical trial is to investigate whether the transplantation of normal myoblasts throughout one muscle (the extensor carpi radialis) of the patients is safe and will improve the strength of that muscle. During this Phase I/II, the patients will be transplanted with myoblasts grown from the muscle biopsy of a donor and kept frozen in liquid nitrogen. Thirty million myoblasts will be injected per cm cube in a progressively higher surface of the radialis (i.e., 3, 6 and 9 cm2). The contralateral muscle will be injected with saline to serve as a control. The strength of both muscles will be measured at 3 months post transplantation to verify whether the myoblast transplantation improved the strength of the muscle. If there is no significant strength improvement, the protocol will be terminated immediately for that patient. If there is a significant strength improvement, the patient will be maintained under immunosuppression until 6 months post transplant and his strength will be re-evaluated.

Conditions

Duchenne Muscular Dystrophy

Study ID

NCT02196467

Start date

May, 2014

Status verified date

Jan, 2021

Completion date

Jan, 2024

Anticipated

Primary completion date

Jan, 2024

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 16+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • A clinical diagnosis of DMD must be confirmed (i.e., with supporting confirmation demonstrated by the identification of a mutation in the dystrophin gene compatible with DMD or presence of less than 10% dystrophin positive fibers in a muscle biopsy in a subject with DMD).
  • The subject has to be older than 16 years of age.
  • Male
  • If on corticosteroids, a stable dose must be maintained for 6 months prior to myoblast transplantation and throughout the trial
  • A potential haplotype compatible donor (the father, the mother, a brother or sister who is more than 18 years old) should be available.
  • The subject must be able to move both wrists, with an MRC scale score of greater than or equal to 2.
  • Subject must have been vaccinated for pneumococcus and Haemophilus influenzae.
  • For subjects who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception for the duration of the study.
  • For subjects that need assisted ventilation, a stable regimen of non-invasive ventilation parameters for 3 months prior to the first myoblast transplantation and anticipation that they will be on a stable regimen throughout the study.
  • Written informed consent of the subject and donor.

Exclusion Criteria:

  • An abnormal sensory examination
  • Persisting abnormal values in a hemogram (red blood cells, white blood cells, hemoglobin or platelets out of laboratory normal range).
  • A history of chronic infection.
  • Abnormal glycosylated hemoglobin level and/or fasting blood glucose (values out of laboratory normal range)
  • Previous neoplasia.
  • Previous tuberculosis or potential carrier of latent tuberculosis.
  • Any clinically significant cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease as determined by the Investigator that is not related to DMD
  • Previous history of renal problems or laboratory analyses suggestive of a renal problem (cystatin C, blood urea nitrogen, electrolytes out of laboratory normal range).
  • Previous biopsies or intramuscular injections in any of the extensor carpi radialis.
  • Subject who participated to phase 1A of myoblast transplantation
  • The subject uses a drug that is not compatible with tacrolimus (see section 6 "Concomitant medications" of protocol) within the last month. If the subject has previously used one of these drugs, the washout period before the onset of tacrolimus should be at least 1 month.
  • Subject tests positive for HIV-1, HIV-2, antigen HIV-1, HBC (hepatitis B surface antigen (HBsAg) and hepatitis B core antigen) HCV, HTLV-1 and anti-HTLV-2.
  • The subject was submitted to electromyography in the extensor carpi radialis, within the last 6 months.
  • There are pre-existing antibodies in the subject serum against the donor lymphocytes.
  • Any change (initiation, dose adjustment, interruption or discontinuation) in any medication that may affect muscle function (eg. Losartan, coenzyme Q10, green tea extract, idebenone, creatine, nutritional supplements, etc.) within 3 months of the first myoblast transplantation.
  • Any change in cardiac medications (ACE inhibitor, beta-blocker, etc.) within 3 months of first myoblast transplantation.
  • Any surgery or fracture of the upper extremity within 3 months prior to first myoblast transplantation or plans to have surgery during the course of the trial.
  • No haplotype compatible donor is available.
  • Unwillingness or inability of the subject to understand and comply with the requirements of this protocol in the opinion of the Investigator or sponsor.
  • Previous tuberculosis or potential carrier of latent tuberculosis.
  • Previous treatment with any other investigational product within 6 months of myoblast transplantation.

Study Design

Enrollment

10 participants

Anticipated

Allocation

Randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Myoblast transplantation & strength

30 million myoblasts will be transplanted per centimeter cube in the Extensor carpi radialis of one of the patient's forearms, resuspended in saline. The strength will be evaluated after 3 and 6 months and the presence of dystrophin after 3 or 6 months.

sham comparator: Saline injection & strength

The same saline solution used in the previous arm, but without cells, will be injected similarly per centimeter cube in the Extensor carpi radialis of the contralateral patient's forearm. The strength will be evaluated after 3 and 6 months and the presence of dystrophin after 3 or 6 months.

Interventions

Myoblast transplantation

30 million myoblasts will be transplanted per centimeter cube in the Extensor carpi radialis of one of the patient's forearm, resuspended in saline (a total of 0.5 ml of suspension per centimetre cube of muscle).

Saline injection

A saline solution (the same used to resuspend de myoblasts in the first intervention) will be injected similarly in the Extensor carpi radialis of the contralateral patient's forearm (a total of 0.5 ml of saline per centimetre cube of muscle).

Primary outcome measure

  • Number of Participants with Serious and Non-Serious Adverse Events as a measure of safety. [ Time Frame: Up to 6 months ]

Central Contacts and Locations

Central contacts

Craig Campbell, MD MSc FRCPC

(519) 685-8332craig.campbell@lhsc.on.ca

Jacques Tremblay, PhD

(418)-525-4444Jacques-P.Tremblay@crchul.ulaval.ca

Locations

Children's Hospital London Health Sciences Centre

Recruiting

London, Ontario, Canada, N6A 4G5

Centre de recherche du CHU de Quebec - CHUL

Recruiting

Quebec, Canada, G1V 4G2

More Information

Sponsor

CHU de Quebec-Universite Laval

Last update posted

Jan 29, 2021

Last verified

Jan, 2021

Keywords

  • myoblast
  • transplantation
  • strength
  • tacrolimus
  • immunosuppression

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by CHU de Quebec-Universite Laval on 2021-01-29.