Nutritional and Metabolic Diseases

Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Musculoskeletal Diseases

Rare Diseases

Obesity

Syndrome

Weight Loss

Body Weight

Brain Neoplasms

Craniopharyngioma

Adamantinoma

Ameloblastoma

Overweight

Overnutrition

Nutrition Disorders

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Bone Neoplasms

Bone Diseases

Hypothalamic Obesity

Neuroepithelioma

All Drugs and Chemicals

Reproductive Control Agents

Hormones

Oxytocin

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

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)

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

Syntocinon

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

Placebo (for Syntocinon)

Shana E McCormack, MD

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.

Intranasal Oxytocin in Hypothalamic Obesity

Intranasal Oxytocin to Promote Weight Loss in Children, Adolescents, and Adults With Brain Tumors and Hypothalamic Obesity Syndrome

Cognitive Restraint at Test Meal Attributable to Oxytocin vs Placebo measured using stop-signal task, stop signal reaction time (SSRT).

For this exploratory outcome, 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 comparison.

Within Participant Difference in Calories Consumed Attributable to Oxytocin vs Placebo Dose 1 (Week 0 \& Week 12). Total number of calories consumed during the standardized test meal.

Within Participant Difference in Calories Consumed Attributable to Oxytocin vs Placebo Dose 2 (Week 2 \& Week 14). Total number of calories consumed during the standardized test meal.

Within Participant Difference After Oxytocin vs After Placebo in Resting Energy Expenditure (kcal/kg lean body mass/day). Resting Energy Expenditure (REE) with output of kcal/kg lean body mass/day measured using indirect calorimetry.

Within Participant Difference After Oxytocin vs Placebo in Respiratory Quotient (RQ) measured using indirect calorimetry.

Total % Body Fat measured using dual energy x-ray absorptiometry (DXA).

Measured using MRI-based post-exercise Creatine Chemical Exchange Saturation Transfer (CrCEST) decline exponential time constant.

Measured using the Dykens Hyperphagia Questionnaire.

The Dykens Hyperphagia Questionnaire is a 11-item questionnaire with responses on a scale of 1 to 5. 1 = Not a Problem, 5 = Severe or Frequent Problem. The scale includes three domains: hyperphagic behavior, hyperphagic drive, and hyperphagic severity. There is also a total or overall score which is calculated by combining the scores from each domain. Maximum Possible Score: 55, Minimum Possible Score: 11. Higher scores indicated more severe and/or frequent Hyperphagia.

Within Participant Change in Disinhibition of Eating Attributable to Oxytocin vs Placebo. Measured using the Eating Inventory questionnaire.

The Eating Inventory consists of 36 statements where participants respond true or false, 14 questions where participants select a response from 1 (least severe: rarely or not at all) to 4 (most severe: always or very much), one final question askes participants to rate their level of restraint in eating from 1 (no restraint) to 6 (constantly limiting food). The scores are assessed in 3 dimensions: Dietary Restraint (Max Score: 21), Disinhibition (Max Score: 16), and Hunger (Max Score: 14).

Within Participant Change in Scores from the Disinhibition of Eating dimension are reported.

The National Institute of Neurological Disorders and Stroke (NINDS) quality of life in neurological disorders (Neuro-QoL) scale is a set of self-reported measures to assess health-related quality of life of adults and children.

Individuals rate domains on a scale from 1 (Never/Not at all) to 5 (Always/Very Often). Each response is assigned a value. Values are combined for a total raw score, then converted to a T-Scores (cohort-specific mean 50, SD 10). Higher scores on the sub-scale domains indicate more of the entity. Adult and child scores were combined in analyses.

Within Participant Change in Family Assessment Device-General Function Scale (FAD-GFS) Attributable to Oxytocin vs Placebo.

The Family Assessment Device (FAD-GFS) includes 12 statements where individuals select from a scale of 4 responses ranging from Strongly Agree (SA) to Strongly Disagree (SD). Each response has a score ranging from 1 to 4, some of the items are reverse scored (i.e. 1 = 4, 2 = 3, 3 = 2, 4 = 1). Minimum Total Score: 12, Maximum Total Score: 48. The scores for each question are added and then divided by the total number of questions. The Minimum Overall Score: 1, Maximum Overall Score: 4. A score of 2 or above is considered dysfunction.

Measured using the Bone Mineral Density in Childhood Study (BMDCS) physical activity questionnaire.

The Bone Mineral Density in Childhood Study (BMDCS) questionnaire captures the amount of time spent in physical activity. The assessment asks participants to record the number of hours spent in different categories of physical activity (Min: 0 hours per week, Max: 11+ hours per week).

Amount of time spent viewing socially relevant versus socially irrelevant stimuli during eye-tracking.

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).

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.

Shana McCormack, MD

Attending Physician

The Safety Monitoring Uniform Report Form (SMURF) was administered at each in-person visit and each telephone check-in visit to assess OXT specific side effects. The full SMURF contains a general inquiry, several questions about daily activities, and modified questions specific to potential OXT side effects.

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

Syntocinon (Intranasal Oxytocin)

1) 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)

Placebo (for Syntocinon): The placebo is identical to the Syntocinon formulation with the exception of the active compound, i.e., without oxytocin.

Placebo

All Participants from Both Treatment Groups.

Overall

1. 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)
2. 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

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

Placebo (for Syntocinon): The placebo is identical to the Syntocinon formulation with the exception of the active compound, i.e., without oxytocin.

Syntocinon (= Oxytocin), Then Placebo

1. 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)
2. 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: The active substance of Syntocinon is a synthetic nonapeptide identical to the posterior pituitary hormone oxytocin.

Placebo (for Syntocinon): The placebo is identical to the Syntocinon formulation with the exception of the active compound, i.e., without oxytocin.

Placebo, Then Syntocinon (= Oxytocin)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

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).

Dr. Shana McCormack

Baseline

Change at 8 Weeks

Within Participant Change in Body Weight with Oxytocin for 8 Weeks

Within Participant Change in Body Weight with Placebo for 8 Weeks

In order to be included, participants needed data in Intervention 1 (Block 1) and Intervention 2 (Block 2). 10 of 13 Participants with complete data available for analysis.

Within Participant Difference After Oxytocin in Peripheral Oxytocin (Area Under the Curve)

Within Participant Difference After Placebo in Peripheral Oxytocin (Area Under the Curve)

In order to be included participants had to have samples collected during both Intervention 1 and Intervention 2. IV Access was not able to be obtained in some individuals. 7 of 13 Participants had data available for analysis. Specimens were collected during the lower dose (Visit 1 or Visit 5) or the higher dose (Visit 2 or Visit 6). As this assessment was only administered once per Intervention, we are not able to calculate/report the change at 8 weeks.

Peripheral Oxytocin Area Under the Curve (AUC)

Within participant difference in response time (msec) on SSRT with Oxytocin

Mixed effects model of other outcomes were also constructed. The "treatment duration" variable reflects the time (in days) in within the treatment Block when the outcome was measured.

Within participant difference in response time (msec) on SSRT with Placebo

Mixed effects model of other outcomes were also constructed. The "treatment duration" variable reflects the time (in days) in within the treatment Block when the outcome was measured.

In order to be included, participants needed data in Intervention 1 (Block 1) and Intervention 2 (Block 2) in order to be included. 11 of 13 Participants with Data for Analysis. As this assessment was only administered once per Intervention, we are not able to calculate/report the change at 8 weeks.

Cognitive Restraint at Test Meal Attributable to Oxytocin vs Placebo

Baseline (Week 0 of Intervention)

Within Participant Difference in Calories Consumed with Oxytocin Dose 1. Total number of kcal eaten, as a % of total kcal offered.

Within Participant Difference in Calories Consumed with Placebo Dose 1. Total number of kcal eaten, as a % of total kcal offered.

In order to be included, participants had to have data in Intervention 1 (Visit 1, Week 0) and Intervention 2 (Visit 5, Week 12). 9 of 13 Participants had data available for analysis. As this assessment was only administered once per Intervention, we are not able to calculate/report the change at 8 weeks.

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

Week 2 of Intervention

Within Participant Difference in Calories Consumed with Oxytocin Dose 2.

Total number of kcal eaten, as a % of total kcal offered.

Within Participant Difference in Calories Consumed with Placebo Dose 2.

Total number of kcal eaten, as a % of total kcal offered.

In order to be included, participants had to have data in Intervention 1 (Visit 2, Week 2) and Intervention 2 (Visit 6, Week 14). 9 of 13 Participants had data available for analysis. As this assessment was only administered once per Intervention, we are not able to calculate/report the change at 8 weeks.

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

End of Intervention

Within Participant Difference After Oxytocin in Resting Energy Expenditure (kcal/kg lean body mass/day) at the end of the Intervention Period (8 Weeks).

Mixed effects model of other outcomes were also constructed. The "treatment duration" variable reflects the time (in days) in within the treatment Block when the outcome was measured.

Within Participant Difference After Placebo in Resting Energy Expenditure (kcal/kg lean body mass/day) at the end of the Intervention Period (8 Weeks).

Mixed effects model of other outcomes were also constructed. The "treatment duration" variable reflects the time (in days) in within the treatment Block when the outcome was measured.

In order to be included, participants had to have data in Intervention 1 (Visit 4, Week 8) and Intervention 2 (Visit 8, Week 20). 9 of 13 Participants had data available for analysis from the end of both treatment blocks.

Within Participant Difference After Oxytocin vs After Placebo in Resting Energy Expenditure (kcal/kg Lean Body Mass/Day)

Within Participant Difference After Oxytocin in Respiratory Quotient (RQ) (VCO2/VO2) at the end of the Intervention (8 Weeks).

Within Participant Difference After Placebo in Respiratory Quotient (RQ) (VCO2/VO2) at the end of the Intervention (8 Weeks).

In order to be included, participants had to have data in Intervention 1 (Visit 4, Week 8) and Intervention 2 (Visit 8, Week 20). 9 of 13 Participants had data available for analysis from the end of both treatment blocks. SSRT was assessed at either the lower dose (Visit 1 or Visit 5) or the higher dose (Visit 2 or Visit 6). As this assessment was only administered once per Intervention, we are not able to calculate/report the change at 8 weeks.

Respiratory Quotient (VCO2/VO2)

Within Participant Difference After Oxytocin in % Body Fat

Linear regression model.

Within Participant Difference After Placebo in % Body Fat

Linear regression model.

In order to be included, participants had to have data in Intervention 1 and Intervention 2. 10 of 13 Participants had data available for analysis. As this assessment was only administered once per Intervention, we are not able to calculate/report the change at 8 weeks.

Within Participant Difference After Oxytocin vs Placebo in % Body Fat

Within Participant Change in Skeletal Muscle Oxidative Phosphorylation Capacity Attributable to Oxytocin vs Placebo

Within Participant Change in Skeletal Muscle OXPHOS Capacity Attributable to Oxytocin vs Placebo

Limited data was collected for the skeletal muscle oxidative phosphorylation capacity. The data requires extensive review for quality prior to analysis. The post-processing requirements are extensive. Analyzed data is not available.

Skeletal Muscle Oxidative Phosphorylation (OXPHOS) Capacity

Within Participant Change in Hyperphagia (Total Score) with Oxytocin for 8 Weeks.

Change in overall score on Hyperphagia Questionnaire.

Within Participant Change in Hyperphagia (Total Score) with Placebo for 8 Weeks.

Change in overall score on Hyperphagia Questionnaire.

Within Participant Change in Hyperphagia (Total Score) Attributable to Oxytocin vs Placebo

Within Participant Change in Disinhibition of Eating with Oxytocin for 8 Weeks. Measured using the Eating Inventory.

Within Participant Change in Disinhibition of Eating with Placebo for 8 Weeks. Measured using the Eating Inventory.

In order to be included, participants needed data in Intervention 1 (Block 1) and Intervention 2 (Block 2). 10 of 13 Participants had complete data available for analysis.

Within Participant Change in Disinhibition of Eating Attributable to Oxytocin vs Placebo

Baseline: Anxiety

Change at 8 Weeks: Anxiety

Baseline: Depression

Change at 8 Weeks: Depression

Baseline: Cognition

Change at 8 Weeks: Cognition

Baseline: Social Function (Adults) or Peer Interaction (Children)

Change at 8 Weeks: Social Function

Within Participant Change in Quality of Life Measures with Oxytocin for 8 Weeks. Measured using the Neuro-QoL scale.

Within Participant Change in Quality of Life Measures with Placebo for 8 Weeks. Measured using the Neuro-QoL scale.

In order to be included, participants had to have data in Intervention 1 and Intervention 2. 11 of 13 Participants had data available for analysis.

Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo

Within Participant Change in Family Assessment Device-General Function Scale (FAD-GRS) with Oxytocin for 8 Weeks

Within Participant Change in Family Assessment Device-General Function Scale (FAD-GRS) with Placebo for 8 Weeks

In order to be included, participants had to have data in Intervention 1 and Intervention 2. 9 of 13 Participants had data available for analysis. This assessment was administered for participants who lived in the same house as the caregiver who would complete the assessment.

Within Participant Change in Family Assessment Device-General Function Scale (FAD-GFS) Attributable to Oxytocin vs Placebo

Median change reported in physical activity, time spent in any activity (hours per week), with Oxytocin.

Median change reported in physical activity, time spent in any activity (hours per week), with Placebo.

In order to be included, participants had to have data in Intervention 1 and Intervention 2. 10 of 13 Participants had data available for analysis.

Within Participant Change in Voluntary Physical Activity Attributable to Oxytocin vs Placebo

Within Participant Change in Eye Tracking Attributable to Oxytocin vs Placebo

Limited data was collected for the Eye Tracking Task. The data requires extensive review for quality prior to analysis. The post-processing requirements are extensive. Analyzed data is not available.

Eye-Tracking Task

EEG task was not completed due to difficulties with equipment. No data collected for analysis.

Spots Global Cancer Trial Database for Intranasal Oxytocin in Hypothalamic Obesity

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Study Description

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