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Not yet recruitingNCT07845994SEMAFORCRANIOUpdated Sep 29, 2026

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

A Phase 3 interventional study of Semaglutide (Wegovy) weekly injection and Placebo weekly Injection in Craniopharyngioma, Child, sponsored by University Hospital, Angers. Not yet recruiting at 17 sites in France. Open to participants aged 12 Years to 17 Years. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by University Hospital, Angers · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
50
Allocation
Randomized
Ages
12 Years to 17 Years
Sex
All
01

Study summary

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).

02

Conditions studied

  • Craniopharyngioma, Child

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Keywords

  • Hypothalamic obesity
  • Pediatric disease
  • Craniopharyngioma
03

Who can participate

Ages eligible
12 Years to 17 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Age 12 to 17 years

Treated craniopharyngioma whose last intervention was >6 months ago and whose tumor is considered stable with :

  • surgical treatmentsurgery for the solid area (non-cystic portion) of the tumor was >6 months ago and whose tumor is considered stable
  • 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

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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
50 participants (estimated)

Study arms

  • Experimental
    SEMAGLUTIDE

    Drug: Semaglutide (Wegovy) weekly injection

  • Placebo comparator
    PLACEBO

    Drug: Placebo weekly Injection

Interventions

  • DrugSemaglutide (Wegovy) weekly injection

    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.

  • DrugPlacebo weekly Injection

    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.

05

What researchers measure

Primary outcomes

  1. Change in BMI SD score (according to french references) at 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

    Time frame: 40 weeks

  2. Change in BMI SD score (according to french references) at 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"

    Time frame: 80 weeks

Secondary outcomes

  1. Change in BMI in kg/m at 40 weeks compared between semaglutide and placebo

    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

    Time frame: 40 weeks

  2. Change in BMI in kg/m at 80 weeks between compared between semaglutide and placebo

    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

    Time frame: 80 weeks

  3. Intra-individual progression of BMI-DS at each visit depending on Semaglutide treatment

    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.

    Time frame: 80 weeks

  4. Effects of 40 weeks of weekly semaglutide treatment on height

    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

    Time frame: 40 weeks

  5. Effects of 40 weeks of weekly semaglutide treatment on weight

    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

    Time frame: 40 weeks

  6. Effects of 40 weeks of weekly semaglutide treatment on waist circumference

    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

    Time frame: 40 weeks

  7. Effects of 40 weeks of weekly semaglutide treatment on arterial blood pressure

    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

    Time frame: 40 weeks

  8. Effects of 40 weeks of weekly semaglutide treatment on fasting blood glucose

    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

    Time frame: 40 weeks

  9. Effects of 40 weeks of weekly semaglutide treatment on HbA1C

    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

    Time frame: 40 weeks

  10. Effects of 40 weeks of weekly semaglutide treatment on insulin level

    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

    Time frame: 40 weeks

  11. Effects of 40 weeks of weekly semaglutide treatment on cholesterol

    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

    Time frame: 40 weeks

  12. Effects of 40 weeks of weekly semaglutide treatment on triglycerides

    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

    Time frame: 40 weeks

  13. Effects of 40 weeks of weekly semaglutide treatment on body composition

    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

    Time frame: 40 weeks

  14. Effects of 40 weeks of weekly semaglutide treatment on bone age

    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

    Time frame: 40 weeks

  15. Effects of 40 weeks of weekly semaglutide treatment on quality of life by PedsQL questionnaire

    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

    Time frame: 40 weeks

  16. Effects of 40 weeks of weekly semaglutide treatment on quality of life by Epworth Sleepiness Scale

    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

    Time frame: 40 weeks

  17. Effects of 40 weeks of weekly semaglutide treatment on quality of life by IWQOL-Kids questionnaire

    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

    Time frame: 40 weeks

  18. Effects of 40 weeks of weekly semaglutide treatment on quality of life by Dykens Hyperphagia questionnaire

    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

    Time frame: 40 weeks

  19. Effects of 40 weeks of weekly semaglutide treatment on quality of life by Daily Hunger Score

    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

    Time frame: 40 weeks

  20. Safety between 2 arms

    Comparison of the incidence of each category of adverse events (AE) between the two arms (semaglutide versus placebo).

    Time frame: 80 weeks

  21. Kinetics of BMI-DS evolution

    Difference in the kinetics of BMI (in DS) evolution depending on whether it occurs in the presence or absence of semaglutide

    Time frame: End of study V10 (106 weeks)

06

Study locations

17 sites
  • Service Endocrinologie pédiatrique, Angers University Hospital
    Angers, France
  • Endocrinologie Pédiatrique, University hospital of Besançon
    Besançon, 25030, France
  • Service d'endocrinologie, diabétoglogie et obésité pédiatrique, Bordeaux University Hospital
    Bordeaux, France
  • Endocrinologie Pédiatrique, Hôpital Femme Mere Enfants, Lyon University Hospital
    Bron, France
  • Département de Pédiatrie, Dijon University Hospital
    Dijon, France
  • Service de Pédiatrie, Grenoble University Hospital
    La Tronche, France
  • Endocrinologie et diabète de l'enfant, Hopital Bicêtre, Paris University Hospital
    Le Kremlin-Bicêtre, France
  • Endocrinologie, diabète et obésité pédiatrique, Lille University Hospital
    Lille, France
  • Service de pédiatrie multidisciplinaire, Hopital La Timone, Marseille University Hospital
    Marseille, France
  • Service de diabétologie et endocrinologie pédiatriques
    Montpellier, France
  • Unité Endocrinologie et Diabète, Nancy University hospital
    Nancy, France
  • Endocrinologie, diabétologie et Gynécologie pédiatrique, Necker Hospital, Paris University Hospital
    Paris, France
  • Service d'endocrinologie diabétologie pédiatrique, Paris University Hospital
    Paris, France
  • Service de Pédiatrie A, Reims University Hospital
    Reims, France
  • Unité d'Endocrinologie et Diabétologie Pédiatriques, Rennes University Hospital
    Rennes, France
  • Service de Pédiatrie, Strasbourg University Hospital
    Strasbourg, France
  • Unité d'Endocrinologie, Maladies Osseuses et Génétique, Toulouse University Hospital
    Toulouse, France
07

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07845994
Lead sponsor
University Hospital, Angers
Responsible party
Sponsor
First posted
Sep 29, 2026
Start date
Nov 2026 (estimated)
Primary completion
Feb 2031 (estimated)
Completion
Feb 2031 (estimated)
Last update
Sep 29, 2026

Study contacts

Regis COUTANT, Professor of Medecine
Contact
ReCoutant@chu-angers.fr
+ 33 (0)2 41 35 56 55
Matthieu LE LAY
Contact
DRCI-Promotion-Interne@chu-angers.fr
+33 (0)2 41 35 58 91
Régis COUTANT, Professor of Medecine
principal investigator · University Hospital of Angers

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
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