Repurposing 5-Azacytidine for the Treatment of Muscle Contractures in Children With Cerebral Palsy

Launched by SHIRLEY RYAN ABILITYLAB · Apr 16, 2024

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ClinConnect Summary

This clinical trial is exploring a medication called 5-azacytidine (AZA) to see if it can help children with cerebral palsy (CP) who have muscle tightness, known as contractures. The researchers want to find out the safest dose of AZA that can improve muscle function and growth. They hope that by using this medication, children with CP can experience better movement and an improved quality of life. Participants will be divided into groups receiving different doses of AZA or a placebo (an inactive substance) and will have up to five visits for medical assessments, blood tests, and a muscle biopsy during a surgery for their contractures.

To be eligible for this study, children must be between 2 and 18 years old, diagnosed with cerebral palsy, and have specific muscle tightness that requires surgery. They also need to have normal kidney and liver function. It’s important for participants who are capable of becoming pregnant to follow specific guidelines regarding contraception during the study. The trial is not yet recruiting participants, but it aims to provide valuable information that could lead to new treatment options for children with CP.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Diagnosis of cerebral palsy.
• • 2. Either achilles or hamstring spasticity with contracture necessitation surgical lengthening.
• • 3. Between 2 and 18 years of age
• • 4. Normal renal and liver function as defined by NCI-CTCAE criteria.71
• • a. Renal Function (Grade 0 - Normal): i. Creatinine: Within the normal range or ≤ 1.0 times the upper limit of normal (ULN).
• • ii. Glomerular filtration rate (GFR): No significant decrease. b. Liver Function (Grade 0 - Normal): i. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT): Within the normal range or ≤ ULN.
• • ii. Total bilirubin: Within the normal range or ≤ 1.0 times ULN
• • 5. A negative pregnancy test for females of childbearing potential\*.
• 6. Females of childbearing potential must agree to use contraception consistently from screening to 6 months after their injection. Highly effective methods of contraception are required for females of childbearing potential:
• • 1. Total abstinence from sexual intercourse.
• • 2. Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS).
• • 3. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, which may be oral, intravaginal, or transdermal used in accordance with medical direction.
• • 4. Progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injected, or implanted, and used in accordance with medical direction.
• 7. Males of childbearing potential\*\* must agree to use contraception consistently from screening until 3 months after the injection. Acceptable methods of contraception for males of childbearing potential are:
• • 1. Total abstinence from sexual intercourse.
• • 2. Condom with spermicide (cream, spray, foam, gel, suppository, or polymer film).
• • Female of childbearing potential is defined as a female capable of becoming pregnant, which includes patients who have had their first menstrual cycle (menarche).
• • Male of childbearing potential is defined as a subject who has reached spermarche.
• Exclusion Criteria:
• • 1. Active infection.
• • 2. Cardiac disease.
• • 3. Allergy to AZA or mannitol.
• • 4. Patient or family who is non-compliant.
• • 5. Received chemotherapy in the preceding three months.
• • 6. Evidence of a hematologic precondition or other malignancy.