Craniopharyngioma, Hypothalamic Obesity
Conditions
Keywords
oxytocin, hypothalamic obesity, craniopharyngioma, metabolism
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.
Interventions
DRUGSyntocinon
The active substance of Syntocinon is a synthetic nonapeptide identical to the posterior pituitary hormone oxytocin.
DRUGPlacebo (for Syntocinon)
The placebo is identical to the Syntocinon formulation with the exception of the active compound, i.e., without oxytocin.
Sponsors
Shana McCormack, MD
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to 35 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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). | 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) | Assessed at the end of each treatment block: Week 8 & Week 20. | 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. |
| Respiratory Quotient (VCO2/VO2) | Assessed at the end of each treatment block: week 8 & week 20. | Within Participant Difference After Oxytocin vs Placebo in Respiratory Quotient (RQ) measured using indirect calorimetry. |
| Within Participant Difference After Oxytocin vs Placebo in % Body Fat | Assessed at the end of each treatment block: week 8 & week 20. | Total % Body Fat measured using dual energy x-ray absorptiometry (DXA). |
| Skeletal Muscle Oxidative Phosphorylation (OXPHOS) Capacity | Assessed at the end of each treatment block. | Measured using MRI-based post-exercise Creatine Chemical Exchange Saturation Transfer (CrCEST) decline exponential time constant. |
| Within Participant Change in Hyperphagia (Total Score) Attributable to Oxytocin vs Placebo | Assessed using data from Intervention 1: Screening and Visit 4 (Week 8) and Intervention 2: Visit 5 (Week 12) and Visit 8 (Week 20). | 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. |
| 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) | 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 Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Assessed using data from Intervention 1: Screening and Visit 4 (Week 8) and Intervention 2: Visit 5 (Week 12) and Visit 8 (Week 20) | 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 | Assessed using data from Intervention 1: Screening and Visit 4 (Week 8) and Intervention 2: Visit 5 (Week 12) and Visit 8 (Week 20). | 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. |
| Within Participant Change in Voluntary Physical Activity Attributable to Oxytocin vs Placebo | Assessed using data from Intervention 1: Screening and Visit 4 (Week 8) and Intervention 2: Visit 5 (Week 12) and Visit 8 (Week 20) | 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). |
| Eye-Tracking Task | Assessed at the end of each treatment block. | Amount of time spent viewing socially relevant versus socially irrelevant stimuli during eye-tracking. |
| EEG Task | Assessed at the end of each treatment block. | N170 EEG signal during eye-tracking |
| Within Participant Change in Disinhibition of Eating Attributable to Oxytocin vs Placebo | Assessed using data from Intervention 1: Screening and Visit 4 (Week 8) and Intervention 2: Visit 5 (Week 12) and Visit 8 (Week 20). | 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. |
| 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 1 (Week 0 & Week 12). Total number of calories consumed during the standardized test meal. |
Countries
United States
Participant flow
Pre-assignment details
Once consent was obtained, participants were reviewed for eligibility and inclusion in the trial. Individuals meeting criteria were randomized. In total, 18 participants signed informed consent and completed in-person screening. 5 of 18 were considered ineligible after screening due to: concomitant medications (2), ECG findings (2), and BMI (1). Intervention Period 1: Week 0 to Week 7, Washout: Week 8 to Week 11, Intervention Period 2: Week 12 to Week 20.
Participants by arm
| Arm | Count |
|---|---|
| Syntocinon (= Oxytocin), Then Placebo 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. | 6 |
| Placebo, Then Syntocinon (= 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)
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. | 7 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (8 Weeks) | Stopping Criteria Met | 0 | 1 |
| Second Intervention (8 Weeks) | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Syntocinon (= Oxytocin), Then Placebo | Total | Placebo, Then Syntocinon (= Oxytocin) |
|---|---|---|---|
| Age, Continuous | 17.0 Years | 15.3 Years | 15.3 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 11 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 11 Participants | 6 Participants |
| Region of Enrollment United States | 6 participants | 13 participants | 7 participants |
| Sex: Female, Male Female | 2 Participants | 6 Participants | 4 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 12 / 12 | 12 / 12 | 12 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
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).
Time frame: 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)
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oxytocin | Weight Loss | Baseline | 88.3 kg |
| Oxytocin | Weight Loss | Change at 8 Weeks | 1.2 kg |
| Placebo | Weight Loss | Change at 8 Weeks | 0.9 kg |
| Placebo | Weight Loss | Baseline | 91.9 kg |
p-value: 0.92Regression, Linear
Secondary
Peripheral Oxytocin Area Under the Curve (AUC)
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.
Time frame: 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.
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oxytocin | Peripheral Oxytocin Area Under the Curve (AUC) | Baseline | 101792 Concentration (min*pg/mL) |
| Oxytocin | Peripheral Oxytocin Area Under the Curve (AUC) | Change at 8 Weeks | NA Concentration (min*pg/mL) |
| Placebo | Peripheral Oxytocin Area Under the Curve (AUC) | Baseline | 99110 Concentration (min*pg/mL) |
| Placebo | Peripheral Oxytocin Area Under the Curve (AUC) | Change at 8 Weeks | NA Concentration (min*pg/mL) |
p-value: 0.57Regression, Linear
Other Pre-specified
Cognitive Restraint at Test Meal Attributable to Oxytocin vs Placebo
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.
Time frame: Intervention 1: Week 2 (Low Dose) or Week 4 (High Dose) and Intervention 2: Week 14 (Low Dose) or Week 16 (High Dose)
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oxytocin | Cognitive Restraint at Test Meal Attributable to Oxytocin vs Placebo | Baseline | 282 msec |
| Oxytocin | Cognitive Restraint at Test Meal Attributable to Oxytocin vs Placebo | Change at 8 Weeks | NA msec |
| Placebo | Cognitive Restraint at Test Meal Attributable to Oxytocin vs Placebo | Baseline | 247 msec |
| Placebo | Cognitive Restraint at Test Meal Attributable to Oxytocin vs Placebo | Change at 8 Weeks | NA msec |
p-value: 0.21Mixed Models Analysis
Other Pre-specified
EEG Task
N170 EEG signal during eye-tracking
Time frame: Assessed at the end of each treatment block.
Population: EEG task was not completed due to difficulties with equipment. No data collected for analysis.
Other Pre-specified
Eye-Tracking Task
Amount of time spent viewing socially relevant versus socially irrelevant stimuli during eye-tracking.
Time frame: Assessed at the end of each treatment block.
Population: 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.
Other Pre-specified
Respiratory Quotient (VCO2/VO2)
Within Participant Difference After Oxytocin vs Placebo in Respiratory Quotient (RQ) measured using indirect calorimetry.
Time frame: Assessed at the end of each treatment block: week 8 & week 20.
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oxytocin | Respiratory Quotient (VCO2/VO2) | End of Intervention | 0.8 Ratio (L C02/L 02) |
| Oxytocin | Respiratory Quotient (VCO2/VO2) | Change at 8 Weeks | NA Ratio (L C02/L 02) |
| Placebo | Respiratory Quotient (VCO2/VO2) | End of Intervention | 0.8 Ratio (L C02/L 02) |
| Placebo | Respiratory Quotient (VCO2/VO2) | Change at 8 Weeks | NA Ratio (L C02/L 02) |
p-value: 0.5Regression, Linear
Other Pre-specified
Skeletal Muscle Oxidative Phosphorylation (OXPHOS) Capacity
Measured using MRI-based post-exercise Creatine Chemical Exchange Saturation Transfer (CrCEST) decline exponential time constant.
Time frame: Assessed at the end of each treatment block.
Population: 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.
Other Pre-specified
Within Participant Change in Disinhibition of Eating Attributable to Oxytocin vs Placebo
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.
Time frame: Assessed using data from Intervention 1: Screening and Visit 4 (Week 8) and Intervention 2: Visit 5 (Week 12) and Visit 8 (Week 20).
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oxytocin | Within Participant Change in Disinhibition of Eating Attributable to Oxytocin vs Placebo | Baseline | 8.5 score on a scale |
| Oxytocin | Within Participant Change in Disinhibition of Eating Attributable to Oxytocin vs Placebo | Change at 8 Weeks | 0 score on a scale |
| Placebo | Within Participant Change in Disinhibition of Eating Attributable to Oxytocin vs Placebo | Baseline | 4 score on a scale |
| Placebo | Within Participant Change in Disinhibition of Eating Attributable to Oxytocin vs Placebo | Change at 8 Weeks | 0 score on a scale |
p-value: 0.52Regression, Linear
Other Pre-specified
Within Participant Change in Family Assessment Device-General Function Scale (FAD-GFS) Attributable to Oxytocin vs Placebo
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.
Time frame: Assessed using data from Intervention 1: Screening and Visit 4 (Week 8) and Intervention 2: Visit 5 (Week 12) and Visit 8 (Week 20).
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oxytocin | Within Participant Change in Family Assessment Device-General Function Scale (FAD-GFS) Attributable to Oxytocin vs Placebo | Baseline | 1.6 score on a scale |
| Oxytocin | Within Participant Change in Family Assessment Device-General Function Scale (FAD-GFS) Attributable to Oxytocin vs Placebo | Change at 8 Weeks | -0.1 score on a scale |
| Placebo | Within Participant Change in Family Assessment Device-General Function Scale (FAD-GFS) Attributable to Oxytocin vs Placebo | Baseline | 1.4 score on a scale |
| Placebo | Within Participant Change in Family Assessment Device-General Function Scale (FAD-GFS) Attributable to Oxytocin vs Placebo | Change at 8 Weeks | 0 score on a scale |
p-value: 0.64Regression, Linear
Other Pre-specified
Within Participant Change in Hyperphagia (Total Score) Attributable to Oxytocin vs Placebo
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.
Time frame: Assessed using data from Intervention 1: Screening and Visit 4 (Week 8) and Intervention 2: Visit 5 (Week 12) and Visit 8 (Week 20).
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oxytocin | Within Participant Change in Hyperphagia (Total Score) Attributable to Oxytocin vs Placebo | Baseline | 20 score on a scale |
| Oxytocin | Within Participant Change in Hyperphagia (Total Score) Attributable to Oxytocin vs Placebo | Change at 8 Weeks | 2 score on a scale |
| Placebo | Within Participant Change in Hyperphagia (Total Score) Attributable to Oxytocin vs Placebo | Baseline | 20.5 score on a scale |
| Placebo | Within Participant Change in Hyperphagia (Total Score) Attributable to Oxytocin vs Placebo | Change at 8 Weeks | 0 score on a scale |
p-value: 0.68Regression, Linear
Other Pre-specified
Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo
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.
Time frame: Assessed using data from Intervention 1: Screening and Visit 4 (Week 8) and Intervention 2: Visit 5 (Week 12) and Visit 8 (Week 20)
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oxytocin | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Baseline: Anxiety | 49.9 T-Score |
| Oxytocin | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Change at 8 Weeks: Anxiety | -2 T-Score |
| Oxytocin | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Baseline: Depression | 42 T-Score |
| Oxytocin | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Change at 8 Weeks: Depression | 0 T-Score |
| Oxytocin | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Baseline: Cognition | 50.4 T-Score |
| Oxytocin | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Change at 8 Weeks: Cognition | 0 T-Score |
| Oxytocin | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Baseline: Social Function (Adults) or Peer Interaction (Children) | 47.9 T-Score |
| Oxytocin | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Change at 8 Weeks: Social Function | -1.6 T-Score |
| Placebo | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Change at 8 Weeks: Social Function | -1.8 T-Score |
| Placebo | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Baseline: Anxiety | 45.7 T-Score |
| Placebo | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Baseline: Cognition | 44 T-Score |
| Placebo | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Change at 8 Weeks: Anxiety | 0 T-Score |
| Placebo | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Baseline: Social Function (Adults) or Peer Interaction (Children) | 47.9 T-Score |
| Placebo | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Baseline: Depression | 36.4 T-Score |
| Placebo | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Change at 8 Weeks: Cognition | 1.2 T-Score |
| Placebo | Within Participant Change in Mental and Emotional Health Related Quality of Life Attributable to Oxytocin vs Placebo | Change at 8 Weeks: Depression | 0 T-Score |
Comparison: Neuro-QoL - Anxietyp-value: 0.91Regression, Linear
Comparison: Neuro-QoL - Depressionp-value: 0.91Regression, Linear
Comparison: Neuro-QoL - Cognitionp-value: 0.04Regression, Linear
Comparison: Neuro-QoL - Social Functionp-value: 0.36Regression, Linear
Other Pre-specified
Within Participant Change in Voluntary Physical Activity Attributable to Oxytocin vs Placebo
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).
Time frame: Assessed using data from Intervention 1: Screening and Visit 4 (Week 8) and Intervention 2: Visit 5 (Week 12) and Visit 8 (Week 20)
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oxytocin | Within Participant Change in Voluntary Physical Activity Attributable to Oxytocin vs Placebo | Baseline | 1.3 hours per week of physical activity |
| Oxytocin | Within Participant Change in Voluntary Physical Activity Attributable to Oxytocin vs Placebo | Change at 8 Weeks | -0.4 hours per week of physical activity |
| Placebo | Within Participant Change in Voluntary Physical Activity Attributable to Oxytocin vs Placebo | Baseline | 1.1 hours per week of physical activity |
| Placebo | Within Participant Change in Voluntary Physical Activity Attributable to Oxytocin vs Placebo | Change at 8 Weeks | -0.1 hours per week of physical activity |
p-value: 0.83Regression, Linear
Other Pre-specified
Within Participant Difference After Oxytocin vs After Placebo in Resting Energy Expenditure (kcal/kg Lean Body Mass/Day)
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.
Time frame: Assessed at the end of each treatment block: Week 8 & Week 20.
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oxytocin | Within Participant Difference After Oxytocin vs After Placebo in Resting Energy Expenditure (kcal/kg Lean Body Mass/Day) | End of Intervention | 129.5 kcal/kg lean mass/day |
| Oxytocin | Within Participant Difference After Oxytocin vs After Placebo in Resting Energy Expenditure (kcal/kg Lean Body Mass/Day) | Change at 8 Weeks | NA kcal/kg lean mass/day |
| Placebo | Within Participant Difference After Oxytocin vs After Placebo in Resting Energy Expenditure (kcal/kg Lean Body Mass/Day) | End of Intervention | 127.2 kcal/kg lean mass/day |
| Placebo | Within Participant Difference After Oxytocin vs After Placebo in Resting Energy Expenditure (kcal/kg Lean Body Mass/Day) | Change at 8 Weeks | NA kcal/kg lean mass/day |
p-value: 0.88Regression, Linear
Other Pre-specified
Within Participant Difference After Oxytocin vs Placebo in % Body Fat
Total % Body Fat measured using dual energy x-ray absorptiometry (DXA).
Time frame: Assessed at the end of each treatment block: week 8 & week 20.
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oxytocin | Within Participant Difference After Oxytocin vs Placebo in % Body Fat | Change at 8 Weeks | NA percent body fat |
| Oxytocin | Within Participant Difference After Oxytocin vs Placebo in % Body Fat | End of Intervention | 50.1 percent body fat |
| Placebo | Within Participant Difference After Oxytocin vs Placebo in % Body Fat | End of Intervention | 50.6 percent body fat |
| Placebo | Within Participant Difference After Oxytocin vs Placebo in % Body Fat | Change at 8 Weeks | NA percent body fat |
p-value: 0.49Regression, Linear
Other Pre-specified
Within Participant Difference in Calories Consumed Attributable to Oxytocin vs Placebo Dose 1 (Week 0 & Week 12), as a % of kcal Offered.
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.
Time frame: Assessed during Intervention 1: Week 0 (Dose 1) and Intervention 2: Week 12 (Dose 1)
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oxytocin | Within Participant Difference in Calories Consumed Attributable to Oxytocin vs Placebo Dose 1 (Week 0 & Week 12), as a % of kcal Offered. | Baseline (Week 0 of Intervention) | 72.4 % of total kcal offered |
| Oxytocin | Within Participant Difference in Calories Consumed Attributable to Oxytocin vs Placebo Dose 1 (Week 0 & Week 12), as a % of kcal Offered. | Change at 8 Weeks | NA % of total kcal offered |
| Placebo | Within Participant Difference in Calories Consumed Attributable to Oxytocin vs Placebo Dose 1 (Week 0 & Week 12), as a % of kcal Offered. | Baseline (Week 0 of Intervention) | 72.6 % of total kcal offered |
| Placebo | Within Participant Difference in Calories Consumed Attributable to Oxytocin vs Placebo Dose 1 (Week 0 & Week 12), as a % of kcal Offered. | Change at 8 Weeks | NA % of total kcal offered |
p-value: 0.55Regression, Linear
Other Pre-specified
Within Participant Difference in Calories Consumed Attributable to Oxytocin vs Placebo Dose 2 (Week 2 & Week 14), as a % of kcal Offered.
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.
Time frame: Assessed during Intervention 1: Week 2 (Dose 2) and Intervention 2: Week 14 (Dose 2).
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oxytocin | Within Participant Difference in Calories Consumed Attributable to Oxytocin vs Placebo Dose 2 (Week 2 & Week 14), as a % of kcal Offered. | Week 2 of Intervention | 72.6 % of total kcal offered |
| Oxytocin | Within Participant Difference in Calories Consumed Attributable to Oxytocin vs Placebo Dose 2 (Week 2 & Week 14), as a % of kcal Offered. | Change at 8 Weeks | NA % of total kcal offered |
| Placebo | Within Participant Difference in Calories Consumed Attributable to Oxytocin vs Placebo Dose 2 (Week 2 & Week 14), as a % of kcal Offered. | Week 2 of Intervention | 67.7 % of total kcal offered |
| Placebo | Within Participant Difference in Calories Consumed Attributable to Oxytocin vs Placebo Dose 2 (Week 2 & Week 14), as a % of kcal Offered. | Change at 8 Weeks | NA % of total kcal offered |
p-value: 0.86Regression, Linear