Intranasal Oxytocin in Hypothalamic Obesity
Condition: Craniopharyngioma; Hypothalamic Obesity
MeSH terms: Craniopharyngioma; Adamantinoma; Obesity
Intervention: Syntocinon; Placebo (for Syntocinon)
Intervention description: The active substance of Syntocinon is a synthetic nonapeptide identical to the posterior pituitary hormone oxytocin.; The placebo is identical to the Syntocinon formulation with the exception of the active compound, i.e., without oxytocin.
Intervention MeSH terms: Oxytocin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 18.0
Sex: All
Minimum age: 10 Years
Maximum age: 35 Years
Healthy volunteers: No
Keywords: oxytocin; hypothalamic obesity; craniopharyngioma; metabolism

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.
    

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.