The Physiologic Effects of Intranasal Oxytocin on Sarcopenic Obesity

Study Overview
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Brief Summary
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Obesity is highly prevalent in older adults and is a major cause of sarcopenia and disability in older adults. Although exercise can counteract the effects of obesity and sarcopenia, many have difficulty adhering to an exercise program and the benefits of exercise are variable. Therefore, there is an urgent need to test novel pharmacologic interventions to prevent disability and loss of independence. Oxytocin is a pituitary hormone released during parturition and lactation that is also known to suppress appetite in rodents and humans; and, recent small studies have found that intranasal oxytocin reduces body weight in adults. We propose a pilot study of intranasal oxytocin as a novel approach to promote weight loss and increase muscle mass in older subjects with sarcopenic obesity.

Detailed Description
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The pilot study will be conducted at 3 sites in 9 visits over a period of 12+ weeks. Older sedentary subjects will be screened for sarcopenic obesity using a modified consensus definition and evaluated at baseline for safety labs, glucose tolerance, body composition, cognition and physical performance, as well as systemic inflammatory markers in blood and muscle tissue. Eligible subjects self-administer 24 IU intranasal oxytocin four times a day for 8 weeks. The study will examine whether the intervention will promote weight loss and preserve muscle mass, thereby preserving and/or improving physical function in older subjects with sarcopenic obesity. Generalized linear mixed effects model will be used to evaluate the effect of oxytocin on the change of each continuous measure. The effect of oxytocin will be assessed by whether the time by oxytocin interaction is significantly different from 0 with a 2-sided p-value<0.05.

Official Title
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The Physiologic Effects of Intranasal Oxytocin on Sarcopenic Obesity

Conditions
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Obesity, Sarcopenic Obesity, Sarcopenia, Aging, Sedentary Lifestyle

Intervention / Treatment
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* Drug: Oxytocin nasal spray
* Drug: Placebo nasal spray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI 30-40 kg/m2 Sedentary (< 2 strenuous exercise/week) Gait speed < 1 meter/second Exclusion Criteria: Diabetes (ADA criteria) Heart disease (MI or New York Heart Classification grade III-IV) Poorly controlled hypertension (SBP > 170 or DBP >95 mm/Hg) Anemia (Hematocrit <34%) Renal Disease (Serum Creatinine >1.4, abnormal serum sodium levels, abnormal urinalysis, or physical exam findings indicative of fluid imbalance; individuals with underlying disorder of sodium/water balance, such as SIADH, diabetes insipidus, or psychogenic polydipsia) Liver Disease (AST/ALT/AlkPhos > 2x upper limit of normal) Use of systemic steroid, androgens, or anti-coagulants Active/unstable conditions: inflammatory, thyroid, autoimmune, gastrointestinal (GI), hematologic, or neoplastic disorders Individuals with underlying seizure disorder or underlying neurologic disorder that increases seizure risk Cognitive impairment (MiniCog <3), unstable mental illness, substance abuse, or history of eating disorder

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxytocin nasal spray<br>Oxytocin (Syntocinon), intranasal, 24IU, 4x a day for 8 weeks, self administered | Drug: Oxytocin nasal spray<br>* Self administered Oxytocin nasal spray q.i.d. for 8 weeks versus placebo (normal saline nasal spray)<br>* Other names: Syntocinon nasal spray;|
| Experimental: Placebo nasal spray<br>Placebo nasal spray, 4x a day for 8 weeks, self administered | Drug: Placebo nasal spray<br>* Self administered Placebo nasal spray q.i.d. for 8 weeks (normal saline nasal spray)<br>* Other names: Saline nasal spray;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight | Intranasal oxytocin will promote weight loss and preserve muscle mass | Baseline to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fat Mass | Pre- and post-measurements of fat mass by dual energy x-ray absorptiometry (DXA) will be examined for individual change with intranasal oxytocin | Baseline to 8 weeks | 
| Change in Body Mass Index | Pre- and post-measurements of lean mass by DXA will be examined for individual change with intranasal oxytocin. Change in body mass index (BMI). | 8 weeks | 
| Change in Glucose Levels Measured Using the Glucose Tolerance Test | Pre- and post-measurements of oral glucose tolerance test for 2-hour plasma glucose will be examined for individual change with intranasal oxytocin | 8 weeks | 
| Change in Short Physical Performance Battery (SPPB) | Pre- and post-measurements will be examined for individual change with intranasal oxytocin. This battery of tests is scored on a scale with 3 SPPB calculation components: Ability to stand for 10 seconds with feet in 3 different positions, scored from 0 min to 4 maximum, with a higher score indicating better balance.(3 Balance subsets: side by side stand scored from 0-1; semi-tandem stance scored from 0-1; tandem stance scored from 0-2) Two timed trials of a 3m or 4 m walk (fastest recorded). Scoring is from 0-4, with 0 being unable to walk and 4 indicating a faster walk time. Time to rise from a chair five times is scored from 0-4, with 0 being unable to complete the activity, and 4 indicating that time to complete is less than 11.1 seconds. Total Score is the sum of all 3 scores: Minimum = 0 Maximum = 12. Higher scores indicate better lower extremity function. Difference between baseline and 8 week performance is reported. | Baseline to 8 weeks | 
| Change in HbA1c (Hemoglobin A1c) | Pre- and post-measurements will be examined for individual change with intranasal oxytocin | Baseline to 8 weeks | 
| Change in Waist Circumference | Pre- and post-measurements will be examined for individual change with intranasal oxytocin | Baseline to 8 weeks | 
| Change in Total Cholesterol | Pre- and post-measurements will be examined for individual change with intranasal oxytocin | Baseline to 8 weeks | 
| Change in Low Density Lipoproteins (LDL) | Pre- and post-measurements will be examined for individual change with intranasal oxytocin | Baseline to 8 weeks | 
| Change in High Density Lipoproteins (HDL) | Pre- and post-measurements will be examined for individual change with intranasal oxytocin | Baseline to 8 weeks | 
| Change in Triglycerides | Pre- and post-measurements will be examined for individual change with intranasal oxytocin | Baseline to 8 weeks | 
| Change in Center for Epidemiologic Studies Scale (CES-D) | Pre- and post-measurements will be examined for individual change with intranasal oxytocin. This is measured on a 20 item scale using the following scoring using number of week days: Rarely or none of the time ( less than 1 day) Some or a little of the time (1-2 days) Occasionally or a moderate amount of time (3-4 days) Most or all of the time (5-7 days) SCORING: zero for answers =1), 1 for answers =2), 2 for answers =3) column, 3 for answers =4) The scoring of positive items is reversed. Possible range of scores is zero to 60, with the higher scores indicating the presence of more symptomatology. | Baseline to 8 weeks | 
| Change in Montreal Cognitive Assessment (MoCA) | Pre- and post-measurements will be examined for individual change with intranasal oxytocin. A 30-point test, with a score of 0 or 1 assigned to each item. The minimum score is 0 and the maximum is 30. The higher the score, the less cognitive impairment. | Baseline to 8 weeks |