SEMAFORCRANIO : Multicenter, Double-blind, Parallel, Randomized Controlled Trial of the Efficacy of Semaglutide in Hypothalamic Obesity Secondary to Craniopharyngioma in Children Aged 12 to 17 Years (SEMAFORCRANIO)
Craniopharyngioma (CP) is a rare embryonic brain tumor of the sellar and parasellar region. Despite its benign histologic characteristics, it is locally aggressive and may cause severe morbidity from invasion into adjacent tissues and structures. Hypothalamic damage due to the tumor or its management is responsible for rapid and massive obesity, one of the most severe sequelae in patients with craniopharyngioma. Current treatment of craniopharyngioma is neurosurgical, possibly completed by radiotherapy. For preventing hypothalamic damage, surgery is the most "sparing" possible for the hypothalamus, possibly completed by a highly conformation radiation treatment, such as proton beam therapy.
Despite these therapeutic advances, obesity remains a significant problem in 30 to 50% of cases today. Most studies showed that the mean BMI at diagnosis of childhood craniopharyngioma was 0.5-0.8 ± 1.5 SD score, the mean BMI gain was +2 to +3 ± 2 SD score within 3 years, with a relative stabilization or a slow increase after 3 years. When there is an anterior and posterior hypothalamic involvement (about 50% of the cases), the mean BMI gain is even higher (+4 ± 3 SD score within 3 years).
Semaglutide, a GLP1RA in weekly injection, has shown its great effectiveness for losing weight in obese adults and adolescents (mean difference in BMI change - 16.7% with semaglutide vs. placebo after 68 weeks). Preliminary data in obese children with craniopharyngioma have shown a mean 25% difference in annual BMI gain (with semaglutide treatment compared to the previous year with no semaglutide in the same children).
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Studientyp
Einschreibung (Geschätzt)
Phase
- Phase 3
Kontakte und Standorte
Studienkontakt
- Name: Regis COUTANT, Professor of Medecine
- Telefonnummer: + 33 (0)2 41 35 56 55
- E-Mail: ReCoutant@chu-angers.fr
Studieren Sie die Kontaktsicherung
- Name: Matthieu LE LAY
- Telefonnummer: +33 (0)2 41 35 58 91
- E-Mail: DRCI-Promotion-Interne@chu-angers.fr
Studienorte
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Angers, Frankreich
- Service Endocrinologie pédiatrique, Angers University Hospital
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Kontakt:
- Régis COUTANT, Professor of Medecine
- Telefonnummer: +33 (0)2.41.35.56.55
- E-Mail: recoutant@chu-angers.fr
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Besançon, Frankreich, 25030
- Endocrinologie Pédiatrique, University hospital of Besançon
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Kontakt:
- Brigitte MIGNOT, Doctor of Medecine
- Telefonnummer: +33(0)3.81.21.91.81
- E-Mail: bmignot@chu-besancon.fr
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Bordeaux, Frankreich
- Service d'endocrinologie, diabétoglogie et obésité pédiatrique, Bordeaux University Hospital
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Kontakt:
- Pascal BARAT, Professor of Medecine
- Telefonnummer: +33(0)5.56.79.87.25
- E-Mail: pascal.barat@chu-bordeaux.fr
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Bron, Frankreich
- Endocrinologie Pédiatrique, Hôpital Femme Mere Enfants, Lyon University Hospital
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Kontakt:
- Carine VILLANUEVA, Doctor of Medecine
- Telefonnummer: +33(0)4.27.85.53.28
- E-Mail: carine.villanueva@chu-lyon.fr
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Dijon, Frankreich
- Département de Pédiatrie, Dijon University Hospital
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Kontakt:
- Candace BEN SIGNOR, Doctor of Medecine
- Telefonnummer: +33(0)3.80.29.30.31
- E-Mail: candace.bensignor@chu-dijon.fr
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La Tronche, Frankreich
- Service de Pédiatrie, Grenoble University Hospital
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Kontakt:
- Cyril RUELLO, Doctor of Medecine
- Telefonnummer: +33(0)4.76.76.89.02
- E-Mail: CRuello1@chu-grenoble.fr
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Le Kremlin-Bicêtre, Frankreich
- Endocrinologie et diabète de l'enfant, Hopital Bicêtre, Paris University Hospital
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Kontakt:
- Cécile TEINTURIER, Doctor of Medecine
- Telefonnummer: +33(0)1.45.21.78.52
- E-Mail: cecile.teinturier@aphp.fr
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Lille, Frankreich
- Endocrinologie, diabète et obésité pédiatrique, Lille University Hospital
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Kontakt:
- Iva GUEORGUIEVA, Doctor of Medecine
- Telefonnummer: +33(0)3.20.44.50.70
- E-Mail: Iva.HUBERT@CHRU-LILLE.FR
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Marseille, Frankreich
- Service de pédiatrie multidisciplinaire, Hopital La Timone, Marseille University Hospital
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Kontakt:
- Rachel REYNAUD, Professor of Medecine
- Telefonnummer: +33(0)4.91.38.83.84
- E-Mail: rachel.reynaud@ap-hm.fr
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Montpellier, Frankreich
- Service de diabétologie et endocrinologie pédiatriques
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Kontakt:
- Essia JOYEZ, Doctor of Medecine
- Telefonnummer: +33(0)4.67.33.65.06
- E-Mail: e-joyez@chu-montpellier.fr
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Nancy, Frankreich
- Unité Endocrinologie et Diabète, Nancy University hospital
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Kontakt:
- Emeline RENARD, Doctor of Medecine
- Telefonnummer: +33(0)3.83.15.53.11
- E-Mail: E.RENARD@chru-nancy.fr
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Paris, Frankreich
- Endocrinologie, diabétologie et Gynécologie pédiatrique, Necker Hospital, Paris University Hospital
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Kontakt:
- Dulanjalee KARIYAWASAM, Doctor of Medecine
- Telefonnummer: +33(0)1.44.49.48.02
- E-Mail: dulanjalee.kariyawasam@aphp.fr
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Paris, Frankreich
- Service d'endocrinologie diabétologie pédiatrique, Paris University Hospital
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Kontakt:
- Ahlam AZAR-KOLAKEZ, Doctor of Medecine
- Telefonnummer: +33(0)1.40.03.41.20
- E-Mail: ahlam.azar-kolakez@aphp.fr
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Reims, Frankreich
- Service de Pédiatrie A, Reims University Hospital
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Kontakt:
- Aurélie BEROT, Doctor of Medecine
- Telefonnummer: +33(0)3.26.78.94.78
- E-Mail: aberot@chu-reims.fr
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Rennes, Frankreich
- Unité d'Endocrinologie et Diabétologie Pédiatriques, Rennes University Hospital
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Kontakt:
- Marie-Béatrice SAADE, Doctor of Medecine
- Telefonnummer: +33(0)2.99.26.71.34
- E-Mail: Marie-beatrice.SAADE@chu-rennes.fr
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Strasbourg, Frankreich
- Service de Pédiatrie, Strasbourg University Hospital
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Kontakt:
- Sylvie ROSSIGNOL, Professor of Medecine
- Telefonnummer: +33(0)3.88.12.77.34
- E-Mail: sylvie.rossignol@chru-strasbourg.fr
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Toulouse, Frankreich
- Unité d'Endocrinologie, Maladies Osseuses et Génétique, Toulouse University Hospital
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Kontakt:
- Thomas EDOUARD, Professor of Medecine
- Telefonnummer: +33(0)5.34.55.85.49
- E-Mail: edouard.t@chu-toulouse.fr
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
- Age 12 to 17 years
Treated craniopharyngioma whose last intervention was >6 months ago and whose tumor is considered stable with :
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surgical treatmentsurgery for the solid area (non-cystic portion) of the tumor was >6 months ago and whose tumor is considered stable
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irradiation treatment
- Appropriate pituitary replacements (including recombinant growth hormone replacement in case of growth hormone deficiency), as assessed by the attending child's physician, according to international recommendations.
- BMI > + 2 SD of the French references (overweight and obesity) or BMI gain ≥ + 1 SD over the past 6 to 12 months (in the absence of overweight or obesity)
- Failure to control weight despite strict adherence to dietary guidelines for at least six months (healthy nutrition and physical activity counseling provided by a dietician or other qualified healthcare professional)
- For women patients with spontaneous menarche (without the use of hormone treatment with oestrogens), highly effective contraceptive methods during all study participation (and until 7 weeks after last study drug intake)
- Subjects covered by or having the rights to medical care assurance
- Written consent signed by the parents or legally acceptable representatives of the subject, and child participation agreement
Exclusion Criteria:
- Other weight loss treatments within 90 days before screening
- Previous surgical treatment for obesity
- Other chronic diseases
- History of pancreatitis (acute or chronic, regardless of the number of years)
- Severe psychiatric disorder (e.g., schizophrenia, bipolar disorder)
- Mental retardation
- A lifetime history of suicidal attempt
- History of NEM2 or medullary thyroid carcinoma, malignant neoplasms/carcinomas in situ, or uncontrolled thyroid disease
- Inability to understand the study
- Major problem of compliance with existing treatments (suggesting that compliance with the protocol will be insufficient)
- Any disorder, unwillingness, or inability, not covered by any of the other exclusion criteria which, in the investigator's opinion, might jeopardize the participant's safety or compliance with the protocol
- Known or suspected abuse of alcohol or recreational drugs
- History of type 1 or type 2 diabetes
- Patient with severe renal insufficiency (eGFR < 30 mL/min/1,73m2)
- Patient with hepatic impairment (mild to severe)
- Participation in another interventional research modifying management or likely to influence the study's assessment criteria
- Pregnancy or desire of pregnancy, breast-feeding patients and parturients
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Vervierfachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
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Placebo-Komparator: PLACEBO
|
A 40-week randomized, placebo double-blind controlled intervention (versus semaglutide injection), followed by an open phase from weeks 40 to 80 where all participants receive semaglutide. In first 40 weeks period (between 0-40 weeks), placebo is initiated in same timing than semaglutide (in other arm). In second 40 weeks period (between 40-80 weeks), Semaglutide is initiated at a dose of 0.25 mg once weekly for the first 4 weeks, followed by escalation every 4 weeks to 0.50, 1.0, 1.70, and 2.40 mg. The recommended target maintenance dose of semaglutide or placebo is 2.4 mg once weekly. Participants are encouraged to reach the recommended semaglutide or placebo target maintenance dose of 2.4 mg once weekly. Those unable to tolerate this dose will be permitted to stay at a lower dose (maximum tolerated dose). At least one attempt to re-escalate to the immediate upper dose is recommended. |
|
Experimental: SEMAGLUTIDE
|
A 40-week randomized, controlled, double-blind semaglutide (versus placebo) intervention (versus placebo), followed by an open phase from weeks 40 to 80 where all participants receive semaglutide. In first 40 weeks period (0-40 weeks), Semaglutide is initiated at a dose of 0.25 mg once weekly for the first 4 weeks, followed by escalation every 4 weeks to 0.50, 1.0, 1.70, and 2.40 mg. In second 40 weeks period (40-80 weeks), Semaglutide is maintened at maximum tolerated dose form 1st period. The recommended target maintenance dose of semaglutide or placebo is 2.4 mg once weekly. Participants are encouraged to reach the recommended semaglutide or placebo target maintenance dose of 2.4 mg once weekly. Those unable to tolerate this dose will be permitted to stay at a lower dose (maximum tolerated dose). At least one attempt to re-escalate to the immediate upper dose is recommended. |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Change in BMI SD score (according to french references) at 40 weeks
Zeitfenster: 40 weeks
|
Co-primary 1 (S40 - RCT): Change in BMI (in SD for age and sex according to French references) after 40 weeks of treatment with semaglutide (dose escalation over 16 weeks followed by a maintenance dose of 2.4 mg/week for 24 weeks) compared to placebo |
40 weeks
|
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Change in BMI SD score (according to french references) at 80 weeks
Zeitfenster: 80 weeks
|
Co-primary 2 (S80 - delayed-start): Change in BMI-SD from baseline to S80: "semaglutide group starting at S0" vs "semaglutide group starting at S40" |
80 weeks
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Change in BMI in kg/m at 40 weeks compared between semaglutide and placebo
Zeitfenster: 40 weeks
|
Evaluation of the variation in Body Mass Index (BMI), expressed in kg/m², from baseline (inclusion) to week 40. This will be compared between two groups: one receiving Semaglutide from the start of the study and the other receiving a placebo for the initial 40 weeks |
40 weeks
|
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Change in BMI in kg/m at 80 weeks between compared between semaglutide and placebo
Zeitfenster: 80 weeks
|
Evaluation of the variation in BMI, expressed in kg/m², from baseline (inclusion) to week 80. This will be compared between two groups: one receiving Semaglutide from the start of the study and the other receiving a placebo for the initial 40 weeks |
80 weeks
|
|
Intra-individual progression of BMI-DS at each visit depending on Semaglutide treatment
Zeitfenster: 80 weeks
|
Intra-individual progression of BMI-SDS values measured at the scheduled visits outlined in the protocol from week 0 to week 80 depending on Semaglutide treatment periods. |
80 weeks
|
|
Effects of 40 weeks of weekly semaglutide treatment on height
Zeitfenster: 40 weeks
|
Comparison of height between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
|
Effects of 40 weeks of weekly semaglutide treatment on weight
Zeitfenster: 40 weeks
|
Comparison of weight between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
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Effects of 40 weeks of weekly semaglutide treatment on waist circumference
Zeitfenster: 40 weeks
|
Comparison of waist circumference between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
|
Effects of 40 weeks of weekly semaglutide treatment on arterial blood pressure
Zeitfenster: 40 weeks
|
Comparison of arterial blood pressure between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
|
Effects of 40 weeks of weekly semaglutide treatment on fasting blood glucose
Zeitfenster: 40 weeks
|
Comparison of fasting blood glucose between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
|
Effects of 40 weeks of weekly semaglutide treatment on HbA1C
Zeitfenster: 40 weeks
|
Comparison of HbA1C between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
|
Effects of 40 weeks of weekly semaglutide treatment on insulin level
Zeitfenster: 40 weeks
|
Comparison of insulin level between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
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Effects of 40 weeks of weekly semaglutide treatment on cholesterol
Zeitfenster: 40 weeks
|
Comparison of cholesterol between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
|
Effects of 40 weeks of weekly semaglutide treatment on triglycerides
Zeitfenster: 40 weeks
|
Comparison of triglycerides between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
|
Effects of 40 weeks of weekly semaglutide treatment on body composition
Zeitfenster: 40 weeks
|
Comparison of body composition (by DEXA) between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
|
Effects of 40 weeks of weekly semaglutide treatment on bone age
Zeitfenster: 40 weeks
|
Comparison of bone age (by X-ray of the left hand and wrist) between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
|
Effects of 40 weeks of weekly semaglutide treatment on quality of life by PedsQL questionnaire
Zeitfenster: 40 weeks
|
Comparison of quality of life by PedsQL questionnaire score between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
|
Effects of 40 weeks of weekly semaglutide treatment on quality of life by Epworth Sleepiness Scale
Zeitfenster: 40 weeks
|
Comparison of quality of life by Epworth Sleepiness Scale score between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
|
Effects of 40 weeks of weekly semaglutide treatment on quality of life by IWQOL-Kids questionnaire
Zeitfenster: 40 weeks
|
Comparison of quality of life by IWQOL-Kids score between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
|
Effects of 40 weeks of weekly semaglutide treatment on quality of life by Dykens Hyperphagia questionnaire
Zeitfenster: 40 weeks
|
Comparison of quality of life by Dykens Hyperphagia questionnaire score between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
|
Effects of 40 weeks of weekly semaglutide treatment on quality of life by Daily Hunger Score
Zeitfenster: 40 weeks
|
Comparison of quality of life by Daily Hunger Score score between patient with 40 weeks of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) versus placebo |
40 weeks
|
|
Safety between 2 arms
Zeitfenster: 80 weeks
|
Comparison of the incidence of each category of adverse events (AE) between the two arms (semaglutide versus placebo). |
80 weeks
|
|
Kinetics of BMI-DS evolution
Zeitfenster: End of study V10 (106 weeks)
|
Difference in the kinetics of BMI (in DS) evolution depending on whether it occurs in the presence or absence of semaglutide |
End of study V10 (106 weeks)
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Hauptermittler: Régis COUTANT, Professor of Medecine, University Hospital of Angers
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Geschätzt)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Urogenitale Erkrankungen
- Erkrankungen des endokrinen Systems
- Neubildungen
- Männliche Urogenitalerkrankungen
- Weibliche Urogenitalerkrankungen
- Weibliche Urogenitalerkrankungen und Schwangerschaftskomplikationen
- Neubildungen nach histologischem Typ
- Gonadenstörungen
- Angeborene Anomalien
- Neuroektodermale Tumoren
- Neoplasmen, Keimzelle und Embryonal
- Neubildungen, Nervengewebe
- Störungen der Geschlechtsentwicklung
- Urogenitale Anomalien
- Gonadendysgenesie
- Hypogonadismus
- Angeborene, erbliche und neonatale Krankheiten und Anomalien
- Kraniopharyngeom
- Sexueller Infantilismus
- Semaglutid
Andere Studien-ID-Nummern
- 49RC23_0307
- 2024-511114-20-00 (Ctis)
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