Intranasal Oxytocin in Hypothalamic Obesity

NCT02849743 | Completed Phase 2 Results DMC

• 1 other identifier: 16-012730
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

Keywords

oxytocin; hypothalamic obesity; craniopharyngioma; metabolism

Outcome Measures

Primary Outcomes (1)

• Weight Loss

  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).

  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)

Secondary Outcomes (1)

• 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.

Other Outcomes (14)

• Cognitive Restraint at Test Meal Attributable to Oxytocin vs Placebo

  Intervention 1: Week 2 (Low Dose) or Week 4 (High Dose) and Intervention 2: Week 14 (Low Dose) or Week 16 (High Dose)

• Within Participant Difference in Calories Consumed Attributable to Oxytocin vs Placebo Dose 1 (Week 0 & Week 12), as a % of kcal Offered.

  Assessed during Intervention 1: Week 0 (Dose 1) and Intervention 2: Week 12 (Dose 1)

• Within Participant Difference in Calories Consumed Attributable to Oxytocin vs Placebo Dose 2 (Week 2 & Week 14), as a % of kcal Offered.

  Assessed during Intervention 1: Week 2 (Dose 2) and Intervention 2: Week 14 (Dose 2).

Study Arms (2)

Syntocinon (= Oxytocin), then Placebo

EXPERIMENTAL

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

Drug: Syntocinon; Drug: Placebo (for Syntocinon)

Placebo, then Syntocinon (= Oxytocin)

EXPERIMENTAL

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)

Drug: Syntocinon; Drug: Placebo (for Syntocinon)

Interventions

Syntocinon DRUG

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

Placebo, then Syntocinon (= Oxytocin); Syntocinon (= Oxytocin), then Placebo

Placebo (for Syntocinon) DRUG

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

Placebo, then Syntocinon (= Oxytocin); Syntocinon (= Oxytocin), then Placebo

Eligibility Criteria

• Age: 10 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Proficient in English.
• Males or females age 10 to 35 years, inclusive.
• Weight ≥ 51 kg.
• 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.
• 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.
• At least 6 months since completion of therapy with stable disease/lack of recurrence.
• 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.)
• Stable for at least 2 months on any appetite-modulating medications (e.g., stimulants).
• Be able to ambulate independently.
• Parental/guardian permission (informed consent) and child assent.

You may not qualify if:

• 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.
• Diabetes mellitus requiring insulin or insulin secretagogue. Laboratory values: HgbA1c ≥8%
• 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.
• 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.
• 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
• History of chronic kidney disease, with screening laboratory studies:
• Laboratory values: eGFR \< 60 mL/min/1.73m2, as defined by the Schwartz formula
• Clinically significant anemia, with screening laboratory studies:
• Laboratory values: Hemoglobin \< 10 g/dL
• Seizure in the past 12 months.
• History of gastrectomy, gastric bypass, small or large bowel resection.
• History of active substance abuse.
• Current psychotic disorder and/or suicidality.
• Supra-physiologic (\>15 mg/m2/day) prescribed doses of hydrocortisone equivalent.

Sponsors & Collaborators

• Shana McCormack, MD: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Craniopharyngioma; Sexual Infantilism

Interventions

Oxytocin

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases; Hypogonadism

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

A new package insert for intranasal oxytocin was released indicating a possible risk for QTc prolongation when administered with other medications known to prolong the QTc. In response with advise from our study cardiologist, we revised exclusion criteria, and added post-dose ECG studies to monitor acute effects. These activities impacted recruitment, as did the COVID-19 pandemic, thus target sample size is less than originally planned (see statistical plan for details).

Results Point of Contact

• Title: Dr. Shana McCormack
• Organization: The Children's Hospital of Philadelphia

mccormacks1@chop.edu

(215) 590-3174

Study Officials

• Shana E McCormack, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Attending Physician

Study Record Dates

• First Submitted: July 22, 2016
• First Posted: July 29, 2016
• Study Start: October 1, 2016
• Primary Completion: April 1, 2021
• Study Completion: May 1, 2022
• Last Updated: October 5, 2022
• Results First Posted: October 5, 2022

Record last verified: 2022-09

Locations

US (1)