Intranasal Oxytocin in Hypothalamic Obesity

Phase 2

Completed

• Conditions: Craniopharyngioma; Hypothalamic Obesity
• Interventions: Drug: Syntocinon; Drug: Placebo (for Syntocinon)

• Registration Number: NCT02849743
• Lead Sponsor: Shana McCormack, MD

Brief Summary

This research study will test if oxytocin, delivered by nasal spray, will promote weight loss in children, adolescents, and adults with Hypothalamic Obesity as compared to a placebo. The study is divided into two parts. During the first part, subjects will receive either oxytocin or placebo. In the second part, subjects will "cross-over" to receive the other treatment - either oxytocin or placebo. During study visits participants will do blood tests, physical exams, metabolic testing, a MRI scan, and some surveys and questionnaires.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2016-07-22
• Study First Submitted QC: 2016-07-26
• Study First Posted: 2016-07-29
• Study Start: 2016-10
• Primary Completion: 2021-04
• Study Completion: 2022-05
• Results First Submitted: 2022-05-04
• Status Verified: 2022-09
• Results First Submitted QC: 2022-09-28
• Last Update Submitted: 2022-09-28
• Results First Posted: 2022-10-05
• Last Update Posted: 2022-10-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

1. Proficient in English.

2. Males or females age 10 to 35 years, inclusive.

3. Weight ≥ 51 kg.

4. Girls must have a negative urine/serum pregnancy test and post-menarchal girls must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study.

5. Hypothalamic obesity, defined for the purposes of this protocol as:

   • previously diagnosed with a brain tumor*
   • currently overweight or obese (BMI > 85%ile for age/sex for < 18 years, BMI > 25 kg/m2 for 18 - 35 years)
   • has at least one other endocrinopathy, indicating hypothalamic damage
   • rate of annualized weight gain during any 6 month period (given variability in clinical course) preceding or after diagnosis and treatment greater than 2 standard deviations above population reference ranges for age and sex.

6. At least 6 months since completion of therapy with stable disease/lack of recurrence.

7. Stable for at least 2 months on any pituitary replacement (e.g., glucocorticoid, thyroid hormone, estrogen/progestin or testosterone, growth hormone, except for adjustments of less than or equal to 20%). (Desmopressin is not required to be stable for 2 months. Participants with DI taking desmopressin are required to have intact thirst and be well-controlled on their current dosing regimen.)

8. Stable for at least 2 months on any appetite-modulating medications (e.g., stimulants).

9. Be able to ambulate independently.

10. Parental/guardian permission (informed consent) and child assent.

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Exclusion Criteria

1. Diabetes insipidus without intact thirst mechanism (i.e., history that participant is not thirsty when hypernatremic and/or continues to be thirsty when hyponatremic, by participant/family and/or practitioner report and medical records) and/or "brittle" diabetes insipidus, defined as requiring >1 admission in the past year and/or any admission within the previous 3 months.

2. Diabetes mellitus requiring insulin or insulin secretagogue. Laboratory values: HgbA1c ≥8%

3. Cardiovascular condition, as defined as any of the following: i) abnormal blood pressure, defined as <3%ile or >97%ile for age, sex and height; ii) history of cardiac arrhythmia or arrhythmia detected on screening ECG; iii) history of heart failure and/or cardiomyopathy; iv) prolonged QTc interval (QTc > 460 msec), and/or long QT syndrome phenotype and/or positive genotype for long QT syndrome pathogenic mutations.

4. Concurrent use of medications known to prolong QTc interval and pose high risk for Torsades de Pointes (TdP) according to the current information available (www.crediblemeds.org). Concomitant medications will be assessed by IDS pharmacist, in collaboration with study cardiologist, if additional clarification is needed. In addition, we require that potential participants be on a stable dose for at least 2 months of any medication with the potential to alter cardiac rhythm to ensure the screening ECG reflects steady-state physiology.

5. History of liver disease, with screening laboratory studies:

   Laboratory values: ALT/SGPT > 3.0X upper limit of normal or AST/SGOT > 3.0X upper limit of normal

6. History of chronic kidney disease, with screening laboratory studies:

   Laboratory values: eGFR < 60 mL/min/1.73m2, as defined by the Schwartz formula

7. Clinically significant anemia, with screening laboratory studies:

   Laboratory values: Hemoglobin < 10 g/dL

8. Seizure in the past 12 months.

9. History of gastrectomy, gastric bypass, small or large bowel resection.

10. History of active substance abuse.

11. Current psychotic disorder and/or suicidality.

12. Supra-physiologic (>15 mg/m2/day) prescribed doses of hydrocortisone equivalent.

13. Anticipated clinical plan to initiate or modify pituitary hormone replacement and/or appetite-modulating drugs during the course of the study.

14. Any investigational drug use within 30 days prior to enrollment.

15. Pregnant or lactating females.

16. Individuals with a known sensitivity to either oxytocin or the components of its formulation.

17. Inability to take an intranasal medication (e.g., recent injury).

18. Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Syntocinon (= Oxytocin), then Placebo	Placebo (for Syntocinon)	Week 0 to Week 7: Intranasal oxytocin, administered 3 times per day (at mealtimes) for 8 weeks (dosage based on weight: 16 IU to 24 IU; dose escalation, if appropriate, occurs at 2 weeks) Week 8 to Week 11: Washout Week 12 to Week 20: Intranasal placebo, administered 3 times per day (at mealtimes) for 8 weeks (dosage based on weight: 16 IU to 24 IU; dose escalation, if appropriate, occurs at 2 weeks) \*Dose Escalation, as appropriate, at 2 Weeks
Placebo, then Syntocinon (= Oxytocin)	Placebo (for Syntocinon)	Week 0 to Week 7: Intranasal placebo, administered 3 times per day (at mealtimes) for 8 weeks (dosage based on weight: 16 IU to 24 IU; dose escalation, if appropriate, occurs at 2 weeks) Week 8 to Week 11: Washout Week 12 to Week 20: Intranasal oxytocin, administered 3 times per day (at mealtimes) for 8 weeks (dosage based on weight: 16 IU to 24 IU; dose escalation, if appropriate, occurs at 2 weeks)
Syntocinon (= Oxytocin), then Placebo	Syntocinon	Week 0 to Week 7: Intranasal oxytocin, administered 3 times per day (at mealtimes) for 8 weeks (dosage based on weight: 16 IU to 24 IU; dose escalation, if appropriate, occurs at 2 weeks) Week 8 to Week 11: Washout Week 12 to Week 20: Intranasal placebo, administered 3 times per day (at mealtimes) for 8 weeks (dosage based on weight: 16 IU to 24 IU; dose escalation, if appropriate, occurs at 2 weeks) \*Dose Escalation, as appropriate, at 2 Weeks
Placebo, then Syntocinon (= Oxytocin)	Syntocinon	Week 0 to Week 7: Intranasal placebo, administered 3 times per day (at mealtimes) for 8 weeks (dosage based on weight: 16 IU to 24 IU; dose escalation, if appropriate, occurs at 2 weeks) Week 8 to Week 11: Washout Week 12 to Week 20: Intranasal oxytocin, administered 3 times per day (at mealtimes) for 8 weeks (dosage based on weight: 16 IU to 24 IU; dose escalation, if appropriate, occurs at 2 weeks)

Primary Outcome Measures

Name	Time	Method
Weight Loss	Assessed at the beginning and end of each Intervention Period (Intervention 1: Visit 1 to Visit 4 = 8 Weeks, Intervention 2: Visit 5 to Visit 8 = 8 Weeks)	The primary objective of this study is to determine whether treatment with 8 weeks of intranasal OXT (relative to 8 weeks of placebo) will promote weight loss in children and adolescents with brain tumors and hypothalamic obesity syndrome ages 10 to 35 years. Specifically, the primary outcome will be: the difference of the post-treatment weight between the two periods (treatment vs. placebo); the statistical model will include the difference of the baseline weight between the two periods and the sequence (OXT-PBO versus PBO-OXT).

Secondary Outcome Measures

Name	Time	Method
Peripheral Oxytocin Area Under the Curve (AUC)	Assessed during each treatment block: at either initial lower dose at baseline (week 0 & week 12) or increased dose at 2 weeks (week 2 & week 15); 50% of participants at each set.	We will determine the immediate peripheral pharmacokinetics of intranasal oxytocin (versus placebo/endogenous oxytocin). In order to minimize participant burden, each participant had the assessment at one time point with either the low or high dose of oxytocin. And at one point during the placebo block.; For this exploratory outcome, visits representing lower dose and higher dose oxytocin were Combined versus lower and higher dose placebo.

Trial Locations

Locations (1)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States