Intranasal Oxytocin in Hypothalamic Obesity

NCT ID: NCT02849743

Last Updated: 2022-10-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2022-05-31

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.

Conditions

Craniopharyngioma; Hypothalamic Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Syntocinon (= Oxytocin), then Placebo

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

Group Type: EXPERIMENTAL

Syntocinon

Intervention Type: DRUG

The active substance of Syntocinon is a synthetic nonapeptide identical to the posterior pituitary hormone oxytocin.

Placebo (for Syntocinon)

Intervention Type: DRUG

The placebo is identical to the Syntocinon formulation with the exception of the active compound, i.e., without oxytocin.

Placebo, then Syntocinon (= Oxytocin)

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)

Group Type: EXPERIMENTAL

Syntocinon

Intervention Type: DRUG

The active substance of Syntocinon is a synthetic nonapeptide identical to the posterior pituitary hormone oxytocin.

Placebo (for Syntocinon)

Intervention Type: DRUG

The placebo is identical to the Syntocinon formulation with the exception of the active compound, i.e., without oxytocin.

Interventions

Syntocinon

The active substance of Syntocinon is a synthetic nonapeptide identical to the posterior pituitary hormone oxytocin.

Intervention Type: DRUG

Placebo (for Syntocinon)

The placebo is identical to the Syntocinon formulation with the exception of the active compound, i.e., without oxytocin.

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shana McCormack, MD

OTHER

Sponsor Role: lead

Responsible Party

Shana McCormack, MD

Attending Physician

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Shana E McCormack, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

16-012730

Identifier Type: -

Identifier Source: org_study_id