Transplantation of Myoblasts to Duchenne Muscular Dystrophy (DMD) Patients
2 other identifiers
interventional
10
1 country
2
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started May 2014
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2014
CompletedFirst Submitted
Initial submission to the registry
May 9, 2014
CompletedFirst Posted
Study publicly available on registry
July 22, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2024
CompletedJanuary 29, 2021
January 1, 2021
9.7 years
May 9, 2014
January 28, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants with Serious and Non-Serious Adverse Events as a measure of safety.
The patients will be monitored for local and systemic potential adverse effects due to the transplantation and for adverse effects associated with immunosuppression with tacrolimus.
Up to 6 months
Secondary Outcomes (3)
Percentage of dystrophin-positive fibers in a muscle biopsy 3 or 6 months after myoblast transplantation.
6 months after the myoblast transplantation
Strength of the Extensor carpi radialis muscles.
At 3 and 6 months after myoblast transplantation.
Presence of a cellular and humoral reaction against the donor antigens
Every 4 weeks after transplantation for 6 months
Study Arms (2)
Myoblast transplantation & strength
EXPERIMENTAL30 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.
Saline injection & strength
SHAM COMPARATORThe 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
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).
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).
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Children's Hospital London Health Sciences Centre
London, Ontario, N6A 4G5, Canada
Centre de recherche du CHU de Quebec - CHUL
Québec, G1V 4G2, Canada
Related Publications (4)
Skuk D, Goulet M, Roy B, Piette V, Cote CH, Chapdelaine P, Hogrel JY, Paradis M, Bouchard JP, Sylvain M, Lachance JG, Tremblay JP. First test of a "high-density injection" protocol for myogenic cell transplantation throughout large volumes of muscles in a Duchenne muscular dystrophy patient: eighteen months follow-up. Neuromuscul Disord. 2007 Jan;17(1):38-46. doi: 10.1016/j.nmd.2006.10.003. Epub 2006 Dec 4.
PMID: 17142039BACKGROUNDSkuk D, Goulet M, Roy B, Chapdelaine P, Bouchard JP, Roy R, Dugre FJ, Sylvain M, Lachance JG, Deschenes L, Senay H, Tremblay JP. Dystrophin expression in muscles of duchenne muscular dystrophy patients after high-density injections of normal myogenic cells. J Neuropathol Exp Neurol. 2006 Apr;65(4):371-86. doi: 10.1097/01.jnen.0000218443.45782.81.
PMID: 16691118BACKGROUNDSkuk D, Vilquin JT, Tremblay JP. Experimental and therapeutic approaches to muscular dystrophies. Curr Opin Neurol. 2002 Oct;15(5):563-9. doi: 10.1097/00019052-200210000-00007.
PMID: 12352000BACKGROUNDHogrel JY, Zagnoli F, Canal A, Fraysse B, Bouchard JP, Skuk D, Fardeau M, Tremblay JP. Assessment of a symptomatic Duchenne muscular dystrophy carrier 20 years after myoblast transplantation from her asymptomatic identical twin sister. Neuromuscul Disord. 2013 Jul;23(7):575-9. doi: 10.1016/j.nmd.2013.04.007. Epub 2013 May 31.
PMID: 23731976BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Craig Campbell, MD MSc FRCPC
University of Western Ontario, Canada
- PRINCIPAL INVESTIGATOR
Jack Puymirat, MD
Centre de recherche du CHU de Quebec
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 9, 2014
First Posted
July 22, 2014
Study Start
May 1, 2014
Primary Completion
January 1, 2024
Study Completion
January 1, 2024
Last Updated
January 29, 2021
Record last verified: 2021-01
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- The data will begin to be available as of the fall of 2019, not being decided yet for how long.
- Access Criteria
- Information to be shared will be the expression of dystrophin, changes in strength, and evidence or not of rejection, in the muscles injected, as well as the side effects observed.
The clinical trial results that have a relation to its objectives will be published as scientific papers in scientific journals or presented at scientific meetings, but without revealing the identity of the participants who will always remain anonymous.