[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100627068":3},{"organization":4,"outcomesModule":7,"designInfo":86,"detailedDescription":93,"studyPopulation":89,"armGroups":94,"interventions":110,"overallOfficials":89,"centralContacts":120,"locations":126,"responsibleParty":146,"collaborators":148,"id":152,"slug":89,"hasResults":153,"nctId":154,"briefTitle":155,"officialTitle":155,"acronym":156,"eligibilityCriteria":157,"healthyVolunteers":158,"sex":159,"minAge":160,"maxAge":161,"enrollmentInfo":162,"targetDuration":89,"studyType":165,"phases":166,"briefSummary":169,"conditions":170,"keywords":172,"overallStatus":129,"whyStopped":89,"lastUpdateSubmitDate":204,"lastUpdatePostDateStruct":205,"startDateStruct":208,"completionDateStruct":210,"leadSponsor":212,"locationsCount":213},{"fullName":5,"class":6},"Unlimited Biotechnology LLC","INDUSTRY",{"primaryOutcomes":8,"secondaryOutcomes":17,"otherOutcomes":30},[9,13],{"measure":10,"description":11,"timeFrame":12},"Number of participants with treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs)","Incidence, severity, and relatedness of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), through Day 90, graded according to CTCAE","Day 1 through Day 90 after AAV administration",{"measure":14,"description":15,"timeFrame":16},"Number of participants with dose-limiting toxicities (DLTs)","Incidence of protocol-defined dose-limiting toxicities (DLTs) within the 21-day DLT observation window following AAV administration","Day 1 through Day 21 after AAV administration",[18,21,24,27],{"measure":19,"description":20,"timeFrame":12},"Number of participants with predefined clinically significant laboratory abnormalities","Number of participants with any of the following laboratory abnormalities through Day 90 (Day 120 for Group 3):\n\nALT or AST \\>3× ULN; Total bilirubin \\>2× ULN; Serum cystatin C ≥1.5× baseline; eGFR decline ≥25% from baseline; Hemoglobin \\\u003C120 g\u002FL in men or \\\u003C110 g\u002FL in women; Hemoglobin decrease ≥2 g\u002FdL; Platelet count \\\u003C100 × 10⁹\u002FL; Neutrophil count \\\u003C1.5 × 10⁹\u002FL; Creatine kinase ≥5× ULN",{"measure":22,"description":23,"timeFrame":12},"Number of participants with new-onset symptomatic heart failure or arrhythmias (CTCAE Grade ≥2)","Number of participants experiencing new-onset symptomatic heart failure or clinically significant arrhythmias graded ≥2 according to CTCAE v5.0 through Day 90 (Day 120 for Group 3)",{"measure":25,"description":26,"timeFrame":12},"Number of participants with injection site reactions","Number of participants experiencing injection site reactions (pain, swelling, erythema, induration, or local inflammation), graded according to CTCAE v5.0, through Day 90 (Day 120 for Group 3)",{"measure":28,"description":29,"timeFrame":12},"Number of participants who discontinue study treatment due to adverse events","Number of participants who discontinue study treatment due to adverse events through Day 90 (Day 120 for Group 3)",[31,35,38,41,44,47,50,53,56,59,62,65,68,71,74,77,80,83],{"measure":32,"description":33,"timeFrame":34},"Change from baseline in Appendicular Lean Mass Index (ALMI) measured by DXA","Change from baseline in Appendicular Lean Mass Index (ALMI) measured by dual-energy X-ray absorptiometry (DXA)","Baseline through Month 12",{"measure":36,"description":37,"timeFrame":34},"Change from baseline in Bone Mineral Density (BMD) measured by DXA (g\u002Fcm²)","Change from baseline in bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA)",{"measure":39,"description":40,"timeFrame":34},"Change from baseline in lower limb one-repetition maximum (1RM) strength (kg)","Change from baseline in maximal voluntary strength assessed by one-repetition maximum (1RM) testing, assessed using leg press 1RM testing",{"measure":42,"description":43,"timeFrame":34},"Change from baseline in grip strength (kg)","Change from baseline in maximal grip strength (kg), assessed using standardized hand dynamometry",{"measure":45,"description":46,"timeFrame":34},"Change from baseline in maximal oxygen uptake (VO₂max, mL\u002Fkg\u002Fmin)","Change from baseline in maximal oxygen uptake (VO₂max, mL\u002Fkg\u002Fmin), assessed by standardized cardiopulmonary exercise testing (CPET)",{"measure":48,"description":49,"timeFrame":34},"Change from baseline in six-minute walk distance (meters)","Change from baseline in distance walked during the six-minute walk test (6MWT), measured in meters",{"measure":51,"description":52,"timeFrame":34},"Change from baseline in Timed Up-and-Go test time (seconds)","Change from baseline in time (seconds) required to complete the Timed Up-and-Go (TUG) test, assessed using standardized procedures",{"measure":54,"description":55,"timeFrame":34},"Change from baseline in Five Times Sit-to-Stand test time (seconds)","Change from baseline in time (seconds) required to complete the Five Times Sit-to-Stand Test (FTSST) under standardized conditions",{"measure":57,"description":58,"timeFrame":34},"Change from baseline in SF-36 Physical and Mental Component Summary scores","Change from baseline in health-related quality of life assessed by the Short Form-36 (SF-36) questionnaire (0-100 scale)",{"measure":60,"description":61,"timeFrame":34},"Change from baseline in Clinical Frailty Scale (CFS) score","Change from baseline in frailty status assessed using the Clinical Frailty Scale (CFS) (1-9 scale)",{"measure":63,"description":64,"timeFrame":34},"Change from baseline in Fried Frailty Phenotype score","Change from baseline in frailty phenotype assessed according to Fried criteria (0-5 scale)",{"measure":66,"description":67,"timeFrame":34},"Change from baseline in serum follistatin concentration (ng\u002Fml)","Change from baseline in serum follistatin levels, measured by enzyme-linked immunosorbent assay (ELISA), ng\u002Fml",{"measure":69,"description":70,"timeFrame":34},"Change from baseline in serum myostatin concentration (ng\u002FmL)","Change from baseline in serum myostatin levels, measured by ELISA, ng\u002Fml",{"measure":72,"description":73,"timeFrame":34},"Change from baseline in serum IGF-1 concentration (ng\u002FmL)","Change from baseline in serum IGF-1 concentration, measured using a validated assay, ng\u002Fml",{"measure":75,"description":76,"timeFrame":34},"Change in mid-arm circumference (cm)","Change from baseline in circumferential measurements (cm) of the mid-arm, assessed using standardized anthropometric techniques",{"measure":78,"description":79,"timeFrame":34},"Change in mid-thigh circumference (cm)","Change from baseline in circumferential measurements (cm) of the mid-thigh, assessed using standardized anthropometric techniques",{"measure":81,"description":82,"timeFrame":34},"Change in calf circumference (cm)","Change from baseline in circumferential measurements (cm) of the calf, assessed using standardized anthropometric techniques",{"measure":84,"description":85,"timeFrame":34},"Change in hip circumference (cm)","Change from baseline in circumferential measurements (cm) of the gluteal (hip) regions, assessed using standardized anthropometric techniques",{"allocation":87,"interventionModel":88,"interventionModelDescription":89,"primaryPurpose":90,"observationalModel":89,"timePerspective":89,"maskingInfo":91},"NON_RANDOMIZED","SEQUENTIAL",null,"PREVENTION",{"masking":92,"maskingDescription":89,"whoMasked":89},"NONE","Approximately 12 participants (with a potential expansion to 18-21) will be sequentially assigned to three cohorts: low-dose AAV-Follistatin monotherapy (n=3), high-dose AAV-Follistatin monotherapy (n=3), or combination therapy (AAV-Follistatin + VEGF plasmid, n=6). A cautious 3+3 dose-escalation design with sentinel dosing will be employed.\n\nAll investigational products are administered via intramuscular injection into large skeletal muscles. In Cohorts 1 and 2, AAV-Follistatin is administered once on Day 1. In Cohort 3, VEGF plasmid is administered on Day 1 and Day 12 (±2 days), followed by AAV-Follistatin on approximately Day 27 (±3 days), corresponding to 15 ± 1 days after the second VEGF plasmid dose.\n\nRapamycin will be administered for approximately two months to mitigate immune responses to the AAV vector. Participants will undergo regular safety monitoring, including clinical assessments, laboratory testing, and strength evaluations.\n\nThe study enrolls adults aged 45-75 years with evidence of age-related muscle decline, who are in generally stable health and able to provide informed consent and comply with study procedures. Eligible participants must demonstrate low or acceptable antibody titers to the AAV vector and hold Próspera ZEDE eResidency or Physical Residency.\n\nKey exclusion criteria include: uncontrolled significant medical conditions; active or recent malignancy; clinically relevant immune disorders or current immunosuppressive therapy; pregnancy or breastfeeding; prior exposure to AAV-based gene therapy; or recent participation in other investigational studies.\n\nScreening (up to 7 days) includes medical history, physical examination, laboratory tests, and baseline muscle assessments (e.g., DXA, strength, and functional testing). The core study period lasts approximately 90 days (for Group 3 = 120 days), with frequent safety assessments and functional evaluations. Participants may opt into extended safety follow-up at approximately 6 and 12 months.\n\nParticipation involves potential risks, including:\n\n* Immune reactions to AAV or follistatin (e.g., flu-like symptoms, elevations in liver enzymes), monitored and managed per protocol;\n* Risks associated with VEGF plasmid (e.g., transient limb pain or swelling);\n* Adverse effects related to rapamycin (e.g., mucositis, metabolic changes, increased infection risk);\n* Unknown or rare risks inherent to gene therapy. Independent safety oversight and predefined stopping rules are in place.\n\nDirect clinical benefit cannot be guaranteed. Participants may experience improvements in muscle mass, strength, endurance, or functional performance; however, this is an early-phase trial primarily designed to assess safety and feasibility. The study may contribute to the development of future therapies for age-related muscle decline.\n\nParticipants should anticipate approximately three months of active participation, with optional follow-up extending to 12 months.",[95,101,105],{"label":96,"type":97,"description":98,"interventionNames":99},"Low-Dose AAV-Follistatin Monotherapy","EXPERIMENTAL","Participants will receive a single intramuscular dose of AAV-Follistatin (5 × 10¹⁰ vg\u002Fkg) on Day 1. The total dose will be administered bilaterally across predefined injection sites in major limb muscles (quadriceps femoris, gluteus maximus, gastrocnemius, and biceps brachii) according to a standardized injection map. Rapamycin will be given per protocol for approximately two months to mitigate immune responses to the AAV vector. This sentinel cohort follows a sequential 3+3 dose-escalation design; dose-limiting toxicities will be assessed through Day 21 prior to escalation to Arm 2.",[100],"Genetic: AAV9-Follistatin gene therapy",{"label":102,"type":97,"description":103,"interventionNames":104},"High-Dose AAV-Follistatin Monotherapy","After safety review of Arm 1, participants in Arm 2 will receive a single higher intramuscular dose of AAV-Follistatin (1 × 10¹¹ vg\u002Fkg) on Day 1, administered bilaterally across predefined injection sites in major limb muscles according to the same standardized injection map. Prophylactic immunomodulation with rapamycin will be provided per protocol for approximately two months, with identical safety monitoring procedures as in Arm 1. This cohort is intended to evaluate dose-dependent safety and tolerability of AAV-Follistatin monotherapy. Dose-limiting toxicities (DLTs) will be assessed through Day 21, and escalation to Arm 3 will proceed following review of safety data and confirmation of predefined criteria.",[100],{"label":106,"type":97,"description":107,"interventionNames":108},"Combination: AAV-Follistatin + VEGF Plasmid","Following safety review of Arm 2, participants in Arm 3 will receive VEGF plasmid (total dose 4.8 mg) administered intramuscularly on Day 1 and Day 12 (±2 days) across the same predefined bilateral muscle groups used for AAV-Follistatin (quadriceps femoris, gluteus maximus, gastrocnemius, and biceps brachii). AAV-Follistatin will then be administered 15 ± 1 days after the second VEGF dose (approximately Day 27-29) using the identical standardized injection map. The AAV dose for Arm 3 will be selected based on safety review of prior cohorts and will be either 5 × 10¹⁰ vg\u002Fkg or 1 × 10¹¹ vg\u002Fkg. Rapamycin will be provided per protocol for approximately two months beginning around the time of AAV administration to mitigate potential immune responses. This cohort evaluates the safety and feasibility of sequential VEGF-mediated vascular support combined with myoanabolic AAV-Follistatin gene therapy.",[100,109],"Genetic: VEGF Plasmid",[111,116],{"type":112,"name":113,"description":114,"armGroupLabels":115,"otherNames":89},"GENETIC","AAV9-Follistatin gene therapy","One-time intramuscular administration of an adeno-associated virus, serotype 9, (AAV9) vector encoding human follistatin.",[106,102,96],{"type":112,"name":117,"description":118,"armGroupLabels":119,"otherNames":89},"VEGF Plasmid","Intramuscular supercoiled plasmid DNA gene therapy encoding vascular endothelial growth factor (VEGF).",[106],[121],{"name":122,"role":123,"phone":124,"phoneExt":89,"email":125},"Ivan Morgunov","CONTACT","+31623454906","ivan@unlimit.bio",[127],{"facility":128,"status":129,"city":130,"state":131,"zip":132,"country":133,"countryCode":134,"cosmosGeoPoint":135,"geoPoint":140,"contacts":141},"GARM","RECRUITING","Coxen Hole","Bay Islands","34101","Honduras","HN",{"type":136,"coordinates":137},"Point",[138,139],-86.53966,16.31553,{"lat":139,"lon":138},[142],{"name":143,"role":123,"phone":144,"phoneExt":89,"email":145},"Mayra Hoch","+504-2408-3544","mayra@garmclinic.com",{"type":147,"investigatorFullName":89,"investigatorTitle":89,"investigatorAffiliation":89,"oldNameTitle":89,"oldOrganization":89},"SPONSOR",[149],{"name":150,"class":151},"Global Alliance for Regenerative Medicine","OTHER","100627068",false,"NCT07443826","CALM-AF-AI: Counteracting Age-related Loss of Muscle With AAV-Follistatin Combined With Angiogenesis-Inducing VEGF Plasmid Gene Therapy","CALM-AF-AI","Inclusion Criteria:\n\n* Voluntary written informed consent obtained prior to any study-related procedures\n* Ability to read, understand, and sign the Informed Consent Form and reliably complete required study documents\n* Willingness to undergo medical intervention, including genetic therapy, and to comply with the visit schedule and all study procedures\n* Commitment to maintain a stable medication and supplement regimen throughout the study, with no initiation of new medications, supplements, or performance-enhancing substances unless approved by the Investigator\n* Men and women aged 45-75 years\n* Body mass index (BMI) between 17.0 and 30.0 kg\u002Fm² at screening\n* Evidence of age-related physical decline or sedentary lifestyle defined as:\n* \\\u003C150 minutes\u002Fweek of moderate-intensity activity, or\n* \\\u003C75 minutes\u002Fweek of vigorous activity, or\n* \\\u003C600 MET-minutes\u002Fweek, or\n* Clinical Frailty Scale (CFS) score 3-6\n* Active Prospera ZEDE eResidency or Physical Residency\n* Stable comorbid conditions for at least 3 months prior to screening\n* Postmenopausal status (women)\n* Willingness to use reliable contraception for 6 months following therapy\n* Low or undetectable antibody titers to AAV9 (≤1:100 by ELISA)\n\nExclusion Criteria:\n\n* Pregnancy, breastfeeding, or intent to become pregnant; premenopausal status (unless ≥12 months amenorrhea or FSH ≥30 IU\u002FL)\n* Subjects who have a history of alcohol or drug abuse within 1 year of study entry\n* Initiation of prohibited medications, supplements, or interventions during the study period that may confound efficacy or safety assessments\n* Active malignancy\n* History of malignancy\n* Strong family history of cancer in first-degree relatives (≥2 relatives with cancer diagnosed \\\u003C60 years)\n* Known hereditary cancer syndrome (BRCA1\u002F2, Lynch syndrome, Li-Fraumeni, FAP, HNPCC) without genetic counseling and enhanced surveillance clearance\n* History of stroke or transient ischemic attack (TIA)\n* History of myocardial infarction (MI) or unstable angina (regardless of time since event)\n* Diagnosed coronary artery disease (CAD) documented by coronary angiography or stress testing\n* Significant atherosclerotic disease at any location (stenosis ≥50% in carotid, femoral, or other major arteries)\n* Prior coronary revascularization (percutaneous coronary intervention \\[PCI\\] or coronary artery bypass grafting \\[CABG\\])\n* Prior valvular repair or replacement\n* History or current diagnosis of heart failure\n* Uncontrolled hypertension (SBP \\>140 mmHg or DBP \\>85 mmHg despite treatment)\n* Left ventricular ejection fraction (LVEF) \\\u003C50%, QTc ≥480 ms, or severe valvular heart disease\n* Ventricular arrhythmias requiring chronic drug treatment or implantable cardioverter-defibrillator\n* Presence of pacemaker or persistent left bundle branch block\n* Known diagnosed cardiomyopathy of any etiology\n* Significant left ventricular hypertrophy, defined as maximal left ventricular wall thickness ≥15 mm in any segment at end-diastole (by echocardiography or cardiac MRI)\n* History of venous thromboembolism (DVT, PE, or thrombosis at any site), particularly if unprovoked, or associated with only minor provoking factors (e.g., minor surgery, combined oral contraceptives, short-term immobilization)\n* Recurrent thrombotic events, including recurrent superficial venous thrombosis\n* Thrombosis at unusual sites (e.g., mesenteric, portal, or splenic vein thrombosis, Cerebral venous sinus thrombosis, Hepatic vein thrombosis (Budd-Chiari syndrome), Renal vein thrombosis, Retinal vein thrombosis)\n* Superior vena cava thrombosis not related to central venous catheterization\n* Strong family history of venous or arterial thrombosis at a young age in first-degree relatives\n* History of recurrent pregnancy loss or severe obstetric complications suggestive of a hypercoagulable state\n* High-degree myopia (≥ -6.0 diopters) or pathological myopia without ophthalmologic clearance\n* History of retinal detachment, vitreous hemorrhage, or retinal vascular disease (diabetic retinopathy, retinal vein occlusion, age-related macular degeneration with neovascularization)\n* Use of systemic anti-VEGF therapy (e.g., bevacizumab)\n* Current use of prohibited medications or supplements (see Section 4.3)\n* Fasting plasma glucose ≥6.0 mmol\u002FL (≥108 mg\u002FdL) at screening\n* HbA1c ≥6.5% (≥48 mmol\u002Fmol) at screening\n* Known history of diabetes mellitus (any type)\n* History of peptic ulcer disease within 12 months\n* Known osteoporosis (DXA T-score ≤ -2.5 at the hip or spine)\n* Severe pulmonary disease, including COPD or restrictive lung disease (FVC \\\u003C49% predicted)\n* Advanced renal disease (CKD stage 3-5, eGFR \\\u003C60 mL\u002Fmin\u002F1.73 m²) or dialysis dependence\n* History of cirrhosis or cholestatic liver disease\n* Chronic viral hepatitis (HBV, HCV)\n* Autoimmune hepatitis\n* Active hepatitis or evidence of hepatic decompensation\n* ALT or AST \\>1.5× upper limit of normal (ULN)\n* Total bilirubin \\>1.5× ULN (unless due to Gilbert's syndrome)\n* Active cholecystitis, symptomatic gallbladder disease (e.g., biliary colic), or any other clinically significant hepatobiliary abnormality\n* Neurodegenerative disease\n* Neuromuscular disorder\n* Psychiatric or movement disorders impairing participation\n* History of drug-induced myopathy or rhabdomyolysis\n* Elevated creatine kinase (CK) at screening CK \\>1.0× ULN confirmed on two separate occasions at least 48 hours apart\n* Systemic lupus erythematosus (SLE), including overlap or drug-induced forms\n* Mixed connective tissue disease (MCTD)\n* Systemic sclerosis (diffuse, limited, or sine scleroderma)\n* Inflammatory myopathies (including polymyositis, dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy, or overlap myositis)\n* Primary Sjögren's syndrome requiring systemic immunosuppression\n* Rheumatoid arthritis requiring biologic therapy or with extra-articular manifestations\n* Undifferentiated connective tissue disease meeting ≥2 classification criteria\n* Current or recent use of immunosuppressive agents (within 3 months)\n* Acute bacterial, fungal, or viral infection, fever, or receipt of live vaccines within 30 days prior to screening\n* Active hepatitis B infection or reactivation risk (HBsAg positive, HBV DNA detectable, or isolated anti-HBc without anti-HBs)\n* Hepatitis C infection (detectable HCV RNA or treatment within 6 months)\n* HIV infection\n* Active or latent tuberculosis (positive QuantiFERON-TB Gold Plus ≥0.35 IU\u002FmL)\n* Acute herpesvirus infection, defined as Active HSV-1 or HSV-2 lesions (vesicles, ulcers, crusts) on clinical examination at screening, CMV or EBV IgM positive\n* Platelet count \\\u003C100 × 10⁹\u002FL at screening\n* Active therapeutic anticoagulation\n* Known inherited or acquired coagulation disorder\n* Use of anticoagulants that cannot be safely discontinued prior to study treatment\n* Severe physical functional limitation (6-Minute Walk Test distance \\\u003C150 meters or CFS\\>6)\n* Prior exposure to any AAV gene therapy product (any AAV serotype)\n* Prior exposure to any investigational drug within 90 days\n* Participation in another clinical trial within 90 days\n* Known hypersensitivity to investigational product components or immunosuppressive agents (e.g., prednisone, rapamycin)\n* Life expectancy \\\u003C6 months\n* Any condition that, in the Investigator's judgment, may pose undue risk, interfere with study outcomes, or impair study participation",true,"ALL","45 Years","75 Years",{"count":163,"type":164},12,"ESTIMATED","INTERVENTIONAL",[167,168],"PHASE1","PHASE2","This Phase 1\u002F2a, open-label, non-randomized study is designed to evaluate the safety and tolerability of intramuscular AAV9-Follistatin gene therapy administered either as monotherapy or in combination with a VEGF-encoding plasmid. Secondary objectives include the assessment of preliminary signals of biological and functional activity, including changes in skeletal muscle mass and performance.",[171],"Age-related Muscle Decline",[173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203],"Sarcopenia","Muscle Atrophy","Skeletal Muscle","Muscle Weakness","Muscle Strength","Aging","Frailty","Follistatin","Myostatin","Viral Vectors","Adeno-Associated Viruses","Activins","Vascular Endothelial Growth Factor A","Angiogenesis Inducing Agents","Plasmids","Intramuscular Injections","Immunosuppression","Prednisolone","Sirolimus","Safety","Dual-Energy X-Ray Absorptiometry","Physical Endurance","Quality of Life","Adults","Middle Aged","Gene Therapy","Grip strength","Rapamycin","6MWT","VO2max","1RM","2026-03-04",{"date":206,"type":207},"2026-03-06","ACTUAL",{"date":209,"type":164},"2026-03-31",{"date":211,"type":164},"2028-06-30",{"name":5,"class":6},1]