5-Azacytidine for Cerebral Palsy

Overseen By Richard L Lieber, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Shirley Ryan AbilityLab

Must not be taking: Chemotherapy

Disqualifiers: Active infection, Cardiac disease, Allergy, others

Compensation: Varies

Number of Visits: 6

Duration: 6-11 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called 5-azacytidine (AZA) to determine if it can help children with cerebral palsy (CP) develop stronger muscles and improve movement. Researchers aim to identify the safest dose of AZA and assess its impact on muscle stem cell function in children with CP. Participants will receive either AZA or a placebo to compare the effects. Eligible children have CP and require surgery for tight muscles in their legs. As a Phase 1 trial, this research focuses on understanding how AZA works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that 5-Azacytidine is likely to be safe for humans?

Research has shown that 5-azacytidine (AZA) is already approved by the FDA for treating conditions like myelodysplastic syndromes, a type of blood disorder, indicating a known safety record in humans. In studies, some patients experienced side effects such as neurotoxicity, which affects the nervous system, but these resolved after stopping the treatment.

In studies with nonhuman primates, researchers examined how AZA moves through the brain and spinal fluid to understand its potential effects in humans. While these results are encouraging, the treatment is still under investigation to determine the safest and most effective dose for children with cerebral palsy (CP). The current trial seeks to identify the optimal dose that is safe and could enhance muscle growth and function in children with CP. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cerebral palsy?

Researchers are excited about 5-Azacytidine for cerebral palsy because it offers a fresh approach to treatment with its unique mechanism of action. Unlike current therapies, which typically focus on managing symptoms through physical therapy and medications like muscle relaxants, 5-Azacytidine works by targeting epigenetic changes. This means it might help modify how genes are expressed in the brain, potentially addressing the underlying issues of cerebral palsy rather than just alleviating symptoms. Furthermore, its administration as a subcutaneous injection could provide a straightforward and less invasive delivery method compared to other more complex treatment regimens.

What evidence suggests that 5-Azacytidine might be an effective treatment for cerebral palsy?

Research suggests that 5-azacytidine (AZA), a drug used for some blood disorders, might aid muscle growth and movement in people with cerebral palsy (CP). Although specific studies on CP are ongoing, AZA has shown promise in improving muscle function by affecting DNA and promoting cell changes. In other conditions, it has increased blood cell levels, suggesting it might also support muscle-generating cells. This trial investigates AZA's effectiveness for this purpose, with participants receiving different dosages of AZA or a placebo to evaluate its impact on muscle growth and movement in children with CP, potentially enhancing their quality of life. ^{1 2 6 7 8}

Who Is on the Research Team?

Andrea Domenighetti, PhD

Principal Investigator

Shirley Ryan AbilityLab

Richard L. Lieber, PhD

Principal Investigator

Shirley Ryan AbilityLab

Patrick Curran, MD

Principal Investigator

Rady Children's Hospital, San Diego

Are You a Good Fit for This Trial?

Children with cerebral palsy who need surgery for muscle contractures can join this trial. They must have normal kidney and liver function, not be pregnant, and either abstain from sex or use certain birth control methods.

Inclusion Criteria

My kidney function is normal, based on my creatinine levels.

I need surgery to lengthen my Achilles or hamstring due to stiffness.

My kidney and liver functions are normal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive a single subcutaneous injection of AZA or placebo and undergo surgery for muscle contracture release

6-11 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including range of motion assessments and wound checks

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• 5-Azacytidine

Trial Overview The study tests different doses of a drug called 5-Azacytidine (AZA) to find the safest amount that might help muscles grow better in kids with CP. It compares these doses against placebos during up to five visits involving blood tests, medical exams, and a muscle biopsy.

How Is the Trial Designed?

Group I: AZA 75mg/m^2 Experimental Treatment 1 Intervention

5-Azacytidine, subcutaneous injection, 75mg/m\^2, one subcutaneous injection for duration of study (estimated at 46 - 76 days)

Group II: AZA 35mg/m^2 Experimental Treatment 1 Intervention

5-Azacytidine, subcutaneous injection, 35mg/m\^2, one subcutaneous injection for duration of study (estimated at 46 - 76 days)

Group III: AZA 20mg/m^2 Experimental Treatment 1 Intervention

5-Azacytidine, subcutaneous injection, 20mg/m\^2, one subcutaneous injection for duration of study (estimated at 46 - 76 days)

Group IV: AZA 10mg/m^2 Experimental Treatment 1 Intervention

5-Azacytidine, subcutaneous injection, 10mg/m\^2, one subcutaneous injection for duration of study (estimated at 46 - 76 days)

Group V: Placebo for 35mg/m^2 Placebo Group 1 Intervention

Placebo, subcutaneous injection, 35mg/m\^2, one subcutaneous injection without the active treatment for duration of study (estimated at 46 - 76 days)

Group VI: Placebo for 20mg/m^2 Placebo Group 1 Intervention

Placebo, subcutaneous injection, 20mg/m\^2, one subcutaneous injection without the active treatment for duration of study (estimated at 46 - 76 days)

Group VII: Placebo for 10mg/m^2 Placebo Group 1 Intervention

Placebo, subcutaneous injection, 10mg/m\^2, one subcutaneous injection without the active treatment for duration of study (estimated at 46 - 76 days)

Group VIII: Placebo for 75mg/m^2 Placebo Group 1 Intervention

Placebo, subcutaneous injection, 75mg/m\^2, one subcutaneous injection without the active treatment for duration of study (estimated at 46 - 76 days)

Who Is Running the Clinical Trial?

Shirley Ryan AbilityLab

Lead Sponsor

Trials

212

Recruited

17,900+

Rady Children's Hospital, San Diego

Collaborator

Trials

42

Recruited

14,300+

Citations

1. withpower.com withpower.com/trial/5-azacytidine-for-cerebral-palsy-c013d

5-Azacytidine for Cerebral Palsy · Info for Participants In this controlled dose-escalation study, we will study the initial safety, biological properties, and potential efficacy of 5-azacytidine (AZA).

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06377085/repurposing-5-azacytidine-for-the-treatment-of-muscle-contractures-in-children-with-cerebral-palsy

Repurposing 5-Azacytidine for the Treatment of Muscle ... In this controlled dose-escalation study, we will study the initial safety, biological properties, and potential efficacy of 5-azacytidine ...

3. cureswithinreach.org cureswithinreach.org/wp-content/uploads/2020/10/Lieber-CALChicago2020_poster.pdf

for Chicago September 15, 2020 While these treatments may slightly reduce disability, they do not prevent or resolve the underlying biological impairment in CP patients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7146732/

Plasma and cerebrospinal fluid pharmacokinetics of the DNA ... IT administration results in pronounced and prolonged 5-AZA CSF exposure above the reported IC 50 range for IDH-mutated glioma cell lines.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11967471/

Clinical efficacy of azacitidine in the treatment of middle ... The overall response rate of the observation group was 66.67%. In terms of blood cells, the observation group's blood cell level after four ...

6. ctv.veeva.com ctv.veeva.com/study/repurposing-5-azacytidine-for-the-treatment-of-muscle-contractures-in-children-with-cerebral-palsy

Repurposing 5-Azacytidine for the Treatment of Muscle ... In this controlled dose-escalation study, we will study the initial safety, biological properties, and potential efficacy of 5-azacytidine ...

7. go.drugbank.com go.drugbank.com/drugs/DB00928

Azacitidine: Uses, Interactions, Mechanism of Action View sample adverse effects data in our new Data Library! See the data ... Cerebral Palsy (CP) / Muscle Contracture · 1, somestatus, stop reason, just ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17596541/

Safety and clinical activity of the combination of 5 ... Dose-limiting toxicity was reversible neurotoxicity. The overall response rate was 42%. In previously untreated older patients, the response ...