Metformin | Pioglitazone | Spironolactone for Early puberty | Accelerated bone maturation | Polycystic ovary syndrome

Inclusion criteria

• {"criterion_text":"- Age at baseline: 8,0 ≤ age ≤ 9,5 years\n- Birth weight for gestational age (BW-GA) in lower tertile: -2,5 ≤ PN-EG Z-score ≤ 0\n- Body mass index for chronological age at 1st visit in upper tercile: +0 ≤ BMI Z-score ≤ +2,5\n- Progressive advanced puberty [bilateral breast development (Tanner stage 2)] of onset between 7,7 and 9,3 years, with a minimum of 2 months progression\n- White ethnicity\n- Term or late preterm pregnancy: 34 ≤ gestational age < 42 weeks\n- Height at 1st visit: 3rd percentile ≤ height ≤ 97th percentile (adjusted for pubertal stage)\n- Written informed consent of parents or legal guardian."}

Exclusion criteria

• {"criterion_text":"- Excessive delay or advancement of bone age (more than 2 years for chronological age). A bone age radiograph taken within the previous 3 months is acceptable for screening purposes. In this case, a new bone age radiograph should be taken within one week before or after the start of treatment.\n- Any disease which, in the opinion of the investigator, compromises the inclusion of the subject in the clinical trial.\n- Tanner's stage of breast development greater than 2.\n- Twin pregnancy\n- Obesity at the 1st visit (BMI Z-score above +2,5 for chronological age)\n- Evidence of a pathological cause of rapid maturation (including but not limited to: congenital adrenal hyperplasia due to 21-hydroxylase deficiency)\n- Known genetic abnormality or chronic conditions, including cardiovascular, neurological, immunological, metabolic, renal, endocrine, digestive, respiratory, or oncological diseases\n- Chronic use of medications, including but not limited to: anticoagulants, anti-inflammatory drugs, oral hypoglycaemics, antiandrogens, oestrogens, progestogens, glucocorticoids, digoxin. Only the use of paracetamol before or during the course of the study will be accepted.\n- Acute infections or intake of antibiotics or anti-inflammatory drugs within the last 14 days. This criterion applies only to blood collections. Blood draws should be postponed for 14 days after the patient no longer has symptoms and stops taking any of these medications.\n- Previous history of hypersensitivity to any of the medicinal products used in the clinical trial, or to their excipients."}

Primary endpoints

• {"endpoint_text":"- Bone age advancement 0-1 year (X-ray of hand and wrist of the left hand) using an automated method, BoneXpert (Visiana, Denmark).","definition_or_measurement_approach":"Measured by X-ray of the left hand and wrist and analysed using the automated BoneXpert method (Visiana, Denmark)."}

Secondary endpoints

• {"endpoint_text":"- Clinical variables: weight, height, BMI, waist and hip circumference and their ratio (incide CC), systolic arterial pressure (SAD), diastolic arterial pressure (DBP) and Tanner stage.","definition_or_measurement_approach":"Standard clinical measurements of anthropometrics and blood pressure; Tanner staging assessed clinically."}
• {"endpoint_text":"- Endocrine-metabolic variables: 1) insulinaemia [fasting glucose, insulin, HOMA-IR (5)]; 2) IGF-I; 3) gonadotropins (LH, FSH); 4) sex steroids [circulating androgens (total testosterone, androstenedione, SHBG, FAI) and oestradiol]; 5) lipids [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides]; 6) markers of inflammation, insulin sensitivity and brown adipose tissue activity [ultrasensitive C-reactive protein (usCRP), GDF-15, HMW-adiponectin, CXCL14].","definition_or_measurement_approach":"Laboratory assays on blood samples: fasting glucose/insulin to compute HOMA-IR, specific assays for IGF-I, LH, FSH, sex steroids, lipid panel, and listed biomarkers (usCRP, GDF-15, HMW-adiponectin, CXCL14)."}
• {"endpoint_text":"- Safety markers: blood count, circulating levels of alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), thyroid stimulating hormone (TSH), urea, creatinine, electrolyte panel, vitamin B12, folic acid.","definition_or_measurement_approach":"Standard clinical laboratory safety panels measured in blood samples."}
• {"endpoint_text":"- Abdominal fat distribution (subcutaneous and visceral area) and liver fat: distribution of abdominal fat and intrahepatic fat shall be analysed by MRI.","definition_or_measurement_approach":"MRI assessment of abdominal fat compartments and intrahepatic fat quantification."}
• {"endpoint_text":"- Additional secondary outcomes: 1) Dietary habits; 2) Tablet acceptability; 3) Adherence study; 4) Adverse events report.","definition_or_measurement_approach":"Questionnaires/interviews for dietary habits and tablet acceptability, adherence assessment methods (not specified), and adverse event reporting per protocol."}

Spain

Earliest CTIS Part Ii Submission Date

23-10-2024

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

520

Number Of Sites

2

Number Of Participants

64

Primary sponsor

Full Name

Hospital Universitari De Girona Doctor Josep Trueta

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Clínica Girona","duties_or_roles":"Magnetic Resonance Imaging (MRI) for the determination of abdominal fat and intrahepatic fat content","organisation_type":"Health care"}
• {"country":"Spain","full_name":"Centro Médico CETIR","duties_or_roles":"Magnetic Resonance Imaging (MRI) for the determination of abdominal fat and intrahepatic fat content.","organisation_type":"Health care"}
• {"country":"Spain","full_name":"Hospital Del Mar","duties_or_roles":"Liquid chromatography mass spectrometry (LC-MS/MS)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Spain","full_name":"Adknoma Health Research S.L.","duties_or_roles":"Sponsor duties codes: 1, 12, 5, 8","organisation_type":"Pharmaceutical company"}