protocolSection identificationModule nctId: NCT06377085, orgStudyIdInfo id: 809325, briefTitle: Repurposing 5-Azacytidine for the Treatment of Muscle Contractures in Children With Cerebral Palsy, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-05, primaryCompletionDateStruct date: 2026-05, completionDateStruct date: 2026-05, studyFirstPostDateStruct date: 2024-04-22, lastUpdatePostDateStruct date: 2024-04-22, sponsorCollaboratorsModule leadSponsor name: Shirley Ryan AbilityLab, class: OTHER, collaborators name: Rady Children's Hospital, San Diego, descriptionModule briefSummary: In this controlled dose-escalation study, we will study the initial safety, biological properties, and potential efficacy of 5-azacytidine (AZA). Our overarching aspiration is for AZA to evolve into an approved pharmacological treatment, fostering muscle growth and enhancing body movement, ultimately contributing to an improved quality of life in children with CP.The main questions this study aims to answer are:1. What is the optimal dose of AZA injection that can be used safely in children with CP?2. Can the optimal safe dose of AZA improve the function of muscle-generating stem cells in children with CP?Each participant will have up to five research visits over the course of the study duration, in which they will participate in: blood draws, pregnancy test(s) (if applicable), medical assessments, and a muscle biopsy during a surgery for muscle contractures.Researchers will compare participants with four different dosages of AZA injections to those with four different dosages of placebo injections. A placebo is a look-alike substance that contains no active drug. They will see if a single injection of AZA at a standard concentration currently approved by the FDA to treat myelodysplastic syndromes, can also safely improve muscle growth and function in children with CP., conditionsModule conditions: Cerebral Palsy, conditions: Contracture, designModule studyType: INTERVENTIONAL, phases: PHASE1, designInfo allocation: NON_RANDOMIZED, interventionModel: SEQUENTIAL, interventionModelDescription: For this Phase 1 trial, we will conduct a dose-escalation study in children having CP who receive 5-Azacytidine (AZA) via a single subcutaneous (SQ) injection two weeks before their surgery, already scheduled to release their contractures. We will use a "3 + 3" dose-escalation design where decisions are based on the rate of toxicity at the current dose level independently from prior dose levels. The primary goal of this study is to determine a Maximum Tolerated Dose (MTD), which will be the highest dose level at which less or equal of 33% of patients experience Dose-Limiting Toxicity (DLT)., primaryPurpose: TREATMENT, maskingInfo masking: TRIPLE, whoMasked: PARTICIPANT, whoMasked: CARE_PROVIDER, whoMasked: OUTCOMES_ASSESSOR, enrollmentInfo count: 27, type: ESTIMATED, armsInterventionsModule interventions name: Placebo for the AZA 10mg/m^2, interventions name: Placebo for the AZA 20mg/m^2, interventions name: Placebo for the AZA 35mg/m^2, interventions name: Placebo for the AZA 75mg/m^2, interventions name: 5-Azacytidine 10mg/m^2, interventions name: 5-Azacytidine 20mg/m^2, interventions name: 5-Azacytidine 35mg/m^2, interventions name: 5-Azacytidine 75mg/m^2, outcomesModule primaryOutcomes measure: Dose-limiting toxicity (DLT)., secondaryOutcomes measure: Satellite Cell Fusion Index., secondaryOutcomes measure: DNA methylation quantification in Satellite Cells and Blood Mononucleated Cells., secondaryOutcomes measure: DNA methylation profiling in Satellite Cells., otherOutcomes measure: Chromatin immunoprecipitation sequencing (ChIP-seq), and assay for transposase-accessible chromatin sequencing (ATAC-seq), eligibilityModule sex: ALL, minimumAge: 2 Years, maximumAge: 18 Years, stdAges: CHILD, stdAges: ADULT, contactsLocationsModule, hasResults: False