Obesity
Conditions
Keywords
weight loss, body mass index, oxytocin, magnetic resonance imaging
Brief summary
This is a randomized, double blind, placebo-controlled study of the effects of intranasal oxytocin in obese adults, ages 18-45 years old. Subjects will be randomized to receive of intranasal oxytocin or placebo (3 sprays per nostril, 4 times per day) for 8 weeks. Study visits include screening to determine eligibility, a 2-part baseline visit, and visits every 2 weeks thereafter until week 14, with a safety follow-up visit 6 weeks after the last dose of study drug. Study procedures include behavioral, metabolic, neuroimaging, and endocrine assessments.
Interventions
DRUGoxytocin nasal spray
oxytocin intranasal spray
DRUGPlacebo
Placebo nasal spray
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* 18-45 years old; * BMI greater than or equal to 30 kg/m2
Exclusion criteria
* Use of drug affecting metabolism, glucose, or appetite (Metformin is allowed if dose and weight are stable for at least 3 months); * history of medication changes within 4 weeks of enrollment; * active substance use; * history of cardiovascular disease, gastrointestinal disorders, bariatric surgery, epilepsy, untreated thyroid disease; * hematocrit \>2% below normal; * fasting glucose \> 125 mg/dL or hemoglobin A1c ≥ 7% ; * ALT or AST \>2.5 times upper limit of normal; * Cr \>1.5 mg/dL; hyponatremia; * pregnancy or breastfeeding; * unwilling to use medically acceptable form of contraception (females only) * follows a nonstandard diet (e.g., gluten free, pescatarian, vegetarian, vegan, Paleo, Atkins, raw diet, macrobiotic diet) * current smoking or tobacco use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Difference in Weight Loss Between Oxytocin and Placebo 8 Weeks After Baseline | Baseline to 8 weeks | The mean difference in weight loss between oxytocin- and placebo-treated groups from baseline to 8 weeks. All participants of the modified intention-to-treat cohort were aggregated into a single linear mixed effects model with the factors Time (Baseline, Week 2, Week 4, Week 6, and Week 8) and Group (oxytocin/placebo) and the interaction Time\*Group controlled for sex (male/female) and obesity class (class I, II, and III) to produce a single value (estimated mean difference) and 95% confidence interval for the difference between groups and a single value (estimated mean change) within each group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Resting Energy Expenditure After 8 Weeks of Oxytocin Versus Placebo | Baseline to 8 weeks | The mean difference in resting energy expenditure between oxytocin- and placebo-treated groups from baseline to 8 weeks. All participants of the modified intention-to-treat cohort were aggregated into a single linear mixed effects model with the factors Time (Baseline and Week 8) and Group (oxytocin/placebo) and the interaction Time\*Group controlled for sex (male/female), obesity class (class I, II, and III), and lean mass to produce a single value (estimated mean difference) and 95% confidence interval for the difference between groups and a single value (estimated mean change) within each group. Reported are model estimates rounded to one decimal. |
| Change in Fat Depots After 8 Weeks of Oxytocin Versus Placebo | Baseline to 8 weeks | The mean difference in total fat mass between oxytocin- and placebo-treated groups from baseline to 8 weeks. All participants of the modified intention-to-treat cohort were aggregated into a single linear mixed effects model with the factors Time (Baseline and Week 8) and Group (oxytocin/placebo) and the interaction Time\*Group controlled for sex (male/female) and obesity class (class I, II, and III) to produce a single value (estimated mean difference) and 95% confidence interval for the difference between groups and a single value (estimated mean change) within each group. |
| Difference in Caloric Intake After 6 Weeks of Oxytocin Versus Placebo | Baseline to 6 weeks | The mean difference in caloric intake between oxytocin- and placebo-treated groups from baseline to 6 weeks. All participants of the modified intention-to-treat cohort were aggregated into a single linear mixed effects model with the factors Time (Baseline and Week 6) and Group (oxytocin/placebo) and the interaction Time\*Group controlled for sex (male/female) and obesity class (class I, II, and III) to produce a single value (estimated mean difference) and 95% confidence interval for the difference between groups and a single value (estimated mean change) within each group. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oxytocin oxytocin nasal spray (24 IU nasal spray, 4 times per day for 8 weeks)
oxytocin nasal spray: oxytocin intranasal spray | 31 |
| Placebo placebo nasal spray (4 times per day for 8 weeks)
Placebo: Placebo nasal spray | 30 |
| Total | 61 |
Baseline characteristics
| Characteristic | Placebo | Total | Oxytocin |
|---|---|---|---|
| Age, Continuous | 33.2 years STANDARD_DEVIATION 6.4 | 33.6 years STANDARD_DEVIATION 6.2 | 34 years STANDARD_DEVIATION 6.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 13 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 48 Participants | 25 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 | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 13 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 38 Participants | 15 Participants |
| Sex: Female, Male Female | 16 Participants | 33 Participants | 17 Participants |
| Sex: Female, Male Male | 14 Participants | 28 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 30 |
| other Total, other adverse events | 24 / 31 | 23 / 30 |
| serious Total, serious adverse events | 0 / 31 | 0 / 30 |
Outcome results
Primary
Mean Difference in Weight Loss Between Oxytocin and Placebo 8 Weeks After Baseline
The mean difference in weight loss between oxytocin- and placebo-treated groups from baseline to 8 weeks. All participants of the modified intention-to-treat cohort were aggregated into a single linear mixed effects model with the factors Time (Baseline, Week 2, Week 4, Week 6, and Week 8) and Group (oxytocin/placebo) and the interaction Time\*Group controlled for sex (male/female) and obesity class (class I, II, and III) to produce a single value (estimated mean difference) and 95% confidence interval for the difference between groups and a single value (estimated mean change) within each group.
Time frame: Baseline to 8 weeks
Population: Modified Intention-To-Treat cohort, which includes all randomly assigned participants who completed at least 1 visit on study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxytocin | Mean Difference in Weight Loss Between Oxytocin and Placebo 8 Weeks After Baseline | 0.20 kilogram |
| Placebo | Mean Difference in Weight Loss Between Oxytocin and Placebo 8 Weeks After Baseline | 0.26 kilogram |
95% CI: [-1.4, 1.3]
Secondary
Change in Fat Depots After 8 Weeks of Oxytocin Versus Placebo
The mean difference in total fat mass between oxytocin- and placebo-treated groups from baseline to 8 weeks. All participants of the modified intention-to-treat cohort were aggregated into a single linear mixed effects model with the factors Time (Baseline and Week 8) and Group (oxytocin/placebo) and the interaction Time\*Group controlled for sex (male/female) and obesity class (class I, II, and III) to produce a single value (estimated mean difference) and 95% confidence interval for the difference between groups and a single value (estimated mean change) within each group.
Time frame: Baseline to 8 weeks
Population: Modified Intention-To-Treat cohort, which includes all randomly assigned participants who completed at least 1 visit on study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxytocin | Change in Fat Depots After 8 Weeks of Oxytocin Versus Placebo | 248.5 gram |
| Placebo | Change in Fat Depots After 8 Weeks of Oxytocin Versus Placebo | 52.5 gram |
95% CI: [-1036, 1428]
Secondary
Change in Resting Energy Expenditure After 8 Weeks of Oxytocin Versus Placebo
The mean difference in resting energy expenditure between oxytocin- and placebo-treated groups from baseline to 8 weeks. All participants of the modified intention-to-treat cohort were aggregated into a single linear mixed effects model with the factors Time (Baseline and Week 8) and Group (oxytocin/placebo) and the interaction Time\*Group controlled for sex (male/female), obesity class (class I, II, and III), and lean mass to produce a single value (estimated mean difference) and 95% confidence interval for the difference between groups and a single value (estimated mean change) within each group. Reported are model estimates rounded to one decimal.
Time frame: Baseline to 8 weeks
Population: Modified Intention-to-Treat cohort, which includes all randomly assigned participants who completed at least 1 visit on study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxytocin | Change in Resting Energy Expenditure After 8 Weeks of Oxytocin Versus Placebo | -17.8 kilocalories/day |
| Placebo | Change in Resting Energy Expenditure After 8 Weeks of Oxytocin Versus Placebo | 11.8 kilocalories/day |
95% CI: [-141.9, 82.6]
Secondary
Difference in Caloric Intake After 6 Weeks of Oxytocin Versus Placebo
The mean difference in caloric intake between oxytocin- and placebo-treated groups from baseline to 6 weeks. All participants of the modified intention-to-treat cohort were aggregated into a single linear mixed effects model with the factors Time (Baseline and Week 6) and Group (oxytocin/placebo) and the interaction Time\*Group controlled for sex (male/female) and obesity class (class I, II, and III) to produce a single value (estimated mean difference) and 95% confidence interval for the difference between groups and a single value (estimated mean change) within each group.
Time frame: Baseline to 6 weeks
Population: Modified Intention-To-Treat cohort, which includes all randomly assigned participants who completed at least 1 visit on study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxytocin | Difference in Caloric Intake After 6 Weeks of Oxytocin Versus Placebo | -31.4 kilocalories |
| Placebo | Difference in Caloric Intake After 6 Weeks of Oxytocin Versus Placebo | 120.6 kilocalories |
95% CI: [-302.3, -1.7]