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).
調査の概要
研究の種類
入学 (推定)
段階
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Regis COUTANT, Professor of Medecine
- 電話番号：+ 33 (0)2 41 35 56 55
- メール：ReCoutant@chu-angers.fr
研究連絡先のバックアップ
- 名前：Matthieu LE LAY
- 電話番号：+33 (0)2 41 35 58 91
- メール：DRCI-Promotion-Interne@chu-angers.fr
研究場所
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Angers、フランス
- Service Endocrinologie pédiatrique, Angers University Hospital
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コンタクト：
- Régis COUTANT, Professor of Medecine
- 電話番号：+33 (0)2.41.35.56.55
- メール：recoutant@chu-angers.fr
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Besançon、フランス、25030
- Endocrinologie Pédiatrique, University hospital of Besançon
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コンタクト：
- Brigitte MIGNOT, Doctor of Medecine
- 電話番号：+33(0)3.81.21.91.81
- メール：bmignot@chu-besancon.fr
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Bordeaux、フランス
- Service d'endocrinologie, diabétoglogie et obésité pédiatrique, Bordeaux University Hospital
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コンタクト：
- Pascal BARAT, Professor of Medecine
- 電話番号：+33(0)5.56.79.87.25
- メール：pascal.barat@chu-bordeaux.fr
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Bron、フランス
- Endocrinologie Pédiatrique, Hôpital Femme Mere Enfants, Lyon University Hospital
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コンタクト：
- Carine VILLANUEVA, Doctor of Medecine
- 電話番号：+33(0)4.27.85.53.28
- メール：carine.villanueva@chu-lyon.fr
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Dijon、フランス
- Département de Pédiatrie, Dijon University Hospital
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コンタクト：
- Candace BEN SIGNOR, Doctor of Medecine
- 電話番号：+33(0)3.80.29.30.31
- メール：candace.bensignor@chu-dijon.fr
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La Tronche、フランス
- Service de Pédiatrie, Grenoble University Hospital
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コンタクト：
- Cyril RUELLO, Doctor of Medecine
- 電話番号：+33(0)4.76.76.89.02
- メール：CRuello1@chu-grenoble.fr
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Le Kremlin-Bicêtre、フランス
- Endocrinologie et diabète de l'enfant, Hopital Bicêtre, Paris University Hospital
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コンタクト：
- Cécile TEINTURIER, Doctor of Medecine
- 電話番号：+33(0)1.45.21.78.52
- メール：cecile.teinturier@aphp.fr
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Lille、フランス
- Endocrinologie, diabète et obésité pédiatrique, Lille University Hospital
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コンタクト：
- Iva GUEORGUIEVA, Doctor of Medecine
- 電話番号：+33(0)3.20.44.50.70
- メール：Iva.HUBERT@CHRU-LILLE.FR
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Marseille、フランス
- Service de pédiatrie multidisciplinaire, Hopital La Timone, Marseille University Hospital
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コンタクト：
- Rachel REYNAUD, Professor of Medecine
- 電話番号：+33(0)4.91.38.83.84
- メール：rachel.reynaud@ap-hm.fr
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Montpellier、フランス
- Service de diabétologie et endocrinologie pédiatriques
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コンタクト：
- Essia JOYEZ, Doctor of Medecine
- 電話番号：+33(0)4.67.33.65.06
- メール：e-joyez@chu-montpellier.fr
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Nancy、フランス
- Unité Endocrinologie et Diabète, Nancy University hospital
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コンタクト：
- Emeline RENARD, Doctor of Medecine
- 電話番号：+33(0)3.83.15.53.11
- メール：E.RENARD@chru-nancy.fr
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Paris、フランス
- Endocrinologie, diabétologie et Gynécologie pédiatrique, Necker Hospital, Paris University Hospital
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コンタクト：
- Dulanjalee KARIYAWASAM, Doctor of Medecine
- 電話番号：+33(0)1.44.49.48.02
- メール：dulanjalee.kariyawasam@aphp.fr
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Paris、フランス
- Service d'endocrinologie diabétologie pédiatrique, Paris University Hospital
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コンタクト：
- Ahlam AZAR-KOLAKEZ, Doctor of Medecine
- 電話番号：+33(0)1.40.03.41.20
- メール：ahlam.azar-kolakez@aphp.fr
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Reims、フランス
- Service de Pédiatrie A, Reims University Hospital
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コンタクト：
- Aurélie BEROT, Doctor of Medecine
- 電話番号：+33(0)3.26.78.94.78
- メール：aberot@chu-reims.fr
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Rennes、フランス
- Unité d'Endocrinologie et Diabétologie Pédiatriques, Rennes University Hospital
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コンタクト：
- Marie-Béatrice SAADE, Doctor of Medecine
- 電話番号：+33(0)2.99.26.71.34
- メール：Marie-beatrice.SAADE@chu-rennes.fr
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Strasbourg、フランス
- Service de Pédiatrie, Strasbourg University Hospital
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コンタクト：
- Sylvie ROSSIGNOL, Professor of Medecine
- 電話番号：+33(0)3.88.12.77.34
- メール：sylvie.rossignol@chru-strasbourg.fr
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Toulouse、フランス
- Unité d'Endocrinologie, Maladies Osseuses et Génétique, Toulouse University Hospital
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コンタクト：
- Thomas EDOUARD, Professor of Medecine
- 電話番号：+33(0)5.34.55.85.49
- メール：edouard.t@chu-toulouse.fr
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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プラセボコンパレーター：プラセボ
|
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. |
|
実験的：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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in BMI SD score (according to french references) at 40 weeks
時間枠：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
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in BMI in kg/m at 40 weeks compared between semaglutide and placebo
時間枠：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
|
|
Change in BMI in kg/m at 80 weeks between compared between semaglutide and placebo
時間枠：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
|
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Intra-individual progression of BMI-DS at each visit depending on Semaglutide treatment
時間枠：80 weeks
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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
|
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Effects of 40 weeks of weekly semaglutide treatment on height
時間枠：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
|
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Effects of 40 weeks of weekly semaglutide treatment on weight
時間枠：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
時間枠：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
|
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Effects of 40 weeks of weekly semaglutide treatment on arterial blood pressure
時間枠：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
|
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Effects of 40 weeks of weekly semaglutide treatment on fasting blood glucose
時間枠：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
|
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Effects of 40 weeks of weekly semaglutide treatment on HbA1C
時間枠：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
|
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Effects of 40 weeks of weekly semaglutide treatment on insulin level
時間枠：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
時間枠：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
|
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Effects of 40 weeks of weekly semaglutide treatment on triglycerides
時間枠：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
|
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Effects of 40 weeks of weekly semaglutide treatment on body composition
時間枠：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
|
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Effects of 40 weeks of weekly semaglutide treatment on bone age
時間枠：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
|
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Effects of 40 weeks of weekly semaglutide treatment on quality of life by PedsQL questionnaire
時間枠：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
|
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Effects of 40 weeks of weekly semaglutide treatment on quality of life by Epworth Sleepiness Scale
時間枠：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
|
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Effects of 40 weeks of weekly semaglutide treatment on quality of life by IWQOL-Kids questionnaire
時間枠：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
|
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Effects of 40 weeks of weekly semaglutide treatment on quality of life by Dykens Hyperphagia questionnaire
時間枠：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
時間枠：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
時間枠：80 weeks
|
Comparison of the incidence of each category of adverse events (AE) between the two arms (semaglutide versus placebo). |
80 weeks
|
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Kinetics of BMI-DS evolution
時間枠：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)
|
協力者と研究者
捜査官
- 主任研究者：Régis COUTANT, Professor of Medecine、University Hospital of Angers
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 49RC23_0307
- 2024-511114-20-00 (Ctis)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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