Sirolimus Effect on Hypertrophic Syndromes Related Gene PIK3CA
- Conditions
- Segmental Overgrowth Disorders Due to PIK3CA
- Registration Number
- NCT02443818
- Lead Sponsor
- Centre Hospitalier Universitaire Dijon
- Brief Summary
It was found that people who have an excessive growth in one or more parts of their body and normal growth in other parts, may have a change in genes responsible for controlling cell growth. This genetic discovery identified a possible treatment for this overgrowth, called Sirolimus.
This is a pilot study, which help the investigators prepare a larger international study, which will aim to determine whether a treatment based Sirolimus is able to stop the excessive growth of one or more parties of their body in people who carry a genetic change in the PIK3CA gene (phosphatidylinosilol-3-kinase encoded by the gene PIK3CA).
- Detailed Description
The duration of participation is 15 months:
* Visit screening: blood test, pre-clinical evaluation, urine collection and chest X-ray.
* First 6 months: participants will have their overgrowth monitored. This step includes 2 visits taking place at the University Hospital of Dijon: complete clinical evaluation, MRI of the body part by the overgrowth and Dual-energy X-ray absorptiometry (DXA).
* Next 6 months: participants will take Sirolimus. This step includes 2 visits (4 and 13 weeks after the start of treatment at local hospital): blood test, urine collection and clinical evaluation.
and 1 end of study visit after 6 months of treatment taking place at the University Hospital of Dijon: blood test, complete clinical evaluation, urine collection, MRI and DXA.
Participants will have several blood and urine tests between visits (1 and 2 weeks after the start of treatment at a local laboratory).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 16
- Post-zygotic PIK3CA mutation
- Age: 3-65 years
- Measurable overgrowth, in current progression or with clinical history of overgrowth progression
- Patient clinically stable
- Presence of a disability, social or cosmetic impairment requiring treatment from the patient perspective,
- Written informed consent form signed and dated by the subject or by the patient's legal representative
- Pregnancy or lactation
- Women and men of reproductive age without any effective method of contraception (during treatment and up to 12 weeks after sirolimus discontinuation)
- Hypersensitivity to the active substance (sirolimus) or to any of the excipients
- Impossibility to obtain written informed consent form signed by the subject or the patient's legal representative, or vulnerable adults
- Treatment with Sirolimus in the last 4 weeks before the trial
- Personal history of malignancy or current investigations for suspected malignancy
- Active skin infection requiring antibiotics or antiviral treatments
- HIV or hepatitis B or C infection
- Past history of Mycobacterium tuberculosis infection
- Active pneumopathy
- Uncontrolled infection
- Chronic liver disease (ASAT or Alanine amino transférase (ALAT)> 3 times upper normal limit)
- Stage 3 (or more) chronic renal insufficiency (eGFR< 60mls/min)
- Neutropenia with neutrophiles < 1.0 x10^9/L
- Uncontrolled dyslipidemia
- Inability to attend study visits
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Measure of the relative percentage of the excess tissue volume evolution at the affected site by volumetric MRI. Change from baseline at 6 and 12 months
- Secondary Outcome Measures
Name Time Method quality of life measured by a questionnaire in the pre- and post-treatment periods At 6 and 12 months The WHO-QOL-BREF questionnaire will be used for adults. For children, PedsQL™ questionnaire for children and parents report for children questionnaires will be used
Measure sites of overgrowth by DXA, MRI and circumferential measurements Change from baseline at 6 and 12 months To determine optimal sirolimus dosing algorithms by plasma assay 12 months Number of hospitalisation and surgery 12 months
Trial Locations
- Locations (11)
CHU d'Angers
🇫🇷Angers, France
CHU de Bordeaux - GH Pellegrin
🇫🇷Bordeaux, France
Hôpital Jeanne de Flandre
🇫🇷Lille, France
CHRU de Montpellier - Hôpital Saint-Eloi
🇫🇷Montpellier, France
Hopitaux de Brabois Chu Nancy
🇫🇷Nancy, France
Hôpital mère-enfant de Nantes
🇫🇷Nantes, France
CHU Paris - Necker
🇫🇷Paris, France
HCL Lyon - CH Lyon Sud
🇫🇷Pierre-Bénite, France
Pôle Cardiovasculaire et Métabolique - Hôpital Larrey
🇫🇷Toulouse, France
CHRU de Tours
🇫🇷Tours, France
CHU de DIJON
🇫🇷Dijon, France