Aging, Obesity, Sarcopenia, Sarcopenic Obesity, Sedentary Lifestyle
Conditions
Brief summary
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
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.
Interventions
DRUGOxytocin nasal spray
Self administered Oxytocin nasal spray q.i.d. for 8 weeks versus placebo (normal saline nasal spray)
DRUGPlacebo nasal spray
Self administered Placebo nasal spray q.i.d. for 8 weeks (normal saline nasal spray)
Sponsors
The University of Texas Health Science Center at San Antonio
The University of Texas Health Science Center, Houston
The University of Texas Medical Branch, Galveston
Sara Espinoza
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight | Baseline to 8 weeks | Intranasal oxytocin will promote weight loss and preserve muscle mass |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Mass Index | 8 weeks | Pre- and post-measurements of lean mass by DXA will be examined for individual change with intranasal oxytocin. Change in body mass index (BMI). |
| Change in Glucose Levels Measured Using the Glucose Tolerance Test | 8 weeks | Pre- and post-measurements of oral glucose tolerance test for 2-hour plasma glucose will be examined for individual change with intranasal oxytocin |
| Change in Short Physical Performance Battery (SPPB) | Baseline to 8 weeks | 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: 1. 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) 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. 3. 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. |
| Change in HbA1c (Hemoglobin A1c) | Baseline to 8 weeks | Pre- and post-measurements will be examined for individual change with intranasal oxytocin |
| Change in Waist Circumference | Baseline to 8 weeks | Pre- and post-measurements will be examined for individual change with intranasal oxytocin |
| Change in Fat Mass | Baseline to 8 weeks | Pre- and post-measurements of fat mass by dual energy x-ray absorptiometry (DXA) will be examined for individual change with intranasal oxytocin |
| Change in Low Density Lipoproteins (LDL) | Baseline to 8 weeks | Pre- and post-measurements will be examined for individual change with intranasal oxytocin |
| Change in High Density Lipoproteins (HDL) | Baseline to 8 weeks | Pre- and post-measurements will be examined for individual change with intranasal oxytocin |
| Change in Triglycerides | Baseline to 8 weeks | Pre- and post-measurements will be examined for individual change with intranasal oxytocin |
| Change in Center for Epidemiologic Studies Scale (CES-D) | Baseline to 8 weeks | 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: 1. Rarely or none of the time ( less than 1 day) 2. Some or a little of the time (1-2 days) 3. Occasionally or a moderate amount of time (3-4 days) 4. 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. |
| Change in Montreal Cognitive Assessment (MoCA) | Baseline to 8 weeks | 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. |
| Change in Total Cholesterol | Baseline to 8 weeks | Pre- and post-measurements will be examined for individual change with intranasal oxytocin |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oxytocin Nasal Spray Oxytocin (Syntocinon), intranasal, 24IU, 4x a day for 8 weeks, self administered
Oxytocin nasal spray: Self administered Oxytocin nasal spray q.i.d. for 8 weeks versus placebo (normal saline nasal spray) | 13 |
| Placebo Nasal Spray Placebo nasal spray, 4x a day for 8 weeks, self administered
Placebo nasal spray: Self administered Placebo nasal spray q.i.d. for 8 weeks (normal saline nasal spray) | 10 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Oxytocin Nasal Spray | Total | Placebo Nasal Spray |
|---|---|---|---|
| Age, Customized Age, 60 or over | 13 Participants | 23 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 20 Participants | 9 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 | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 11 Participants | 18 Participants | 7 Participants |
| Region of Enrollment United States | 13 participants | 23 participants | 10 participants |
| Sex: Female, Male Female | 8 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 9 |
| other Total, other adverse events | 12 / 12 | 9 / 9 |
| serious Total, serious adverse events | 0 / 12 | 0 / 9 |
Outcome results
Primary
Change in Body Weight
Intranasal oxytocin will promote weight loss and preserve muscle mass
Time frame: Baseline to 8 weeks
Population: Two participants withdrew after randomization; 1 in Oxytocin and 1 in Placebo group. Data from these two subjects were not collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in Body Weight | 0.54 Kilograms | Standard Deviation 1.6 |
| Placebo Nasal Spray | Change in Body Weight | 0.04 Kilograms | Standard Deviation 2.5 |
Secondary
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).
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in Body Mass Index | 36.8 kg/m2 | Standard Deviation 3.5 |
| Placebo Nasal Spray | Change in Body Mass Index | 36.8 kg/m2 | Standard Deviation 3.6 |
Secondary
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: 1. Rarely or none of the time ( less than 1 day) 2. Some or a little of the time (1-2 days) 3. Occasionally or a moderate amount of time (3-4 days) 4. 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.
Time frame: Baseline to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in Center for Epidemiologic Studies Scale (CES-D) | -1.375 score on a scale | Standard Deviation 2.186 |
| Placebo Nasal Spray | Change in Center for Epidemiologic Studies Scale (CES-D) | 0.2222 score on a scale | Standard Deviation 2.7285 |
Secondary
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
Time frame: Baseline to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in Fat Mass | -0.2 Kilograms | Standard Deviation 0.99 |
| Placebo Nasal Spray | Change in Fat Mass | -0.1 Kilograms | Standard Deviation 0.92 |
Secondary
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
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin Nasal Spray | Change in Glucose Levels Measured Using the Glucose Tolerance Test | Fasting glucose | 3.36 mg/dL | Standard Deviation 10.18 |
| Oxytocin Nasal Spray | Change in Glucose Levels Measured Using the Glucose Tolerance Test | 2-hour glucose | -3.15 mg/dL | Standard Deviation 31.126 |
| Placebo Nasal Spray | Change in Glucose Levels Measured Using the Glucose Tolerance Test | Fasting glucose | 2.85 mg/dL | Standard Deviation 6.28 |
| Placebo Nasal Spray | Change in Glucose Levels Measured Using the Glucose Tolerance Test | 2-hour glucose | -3.375 mg/dL | Standard Deviation 14.88 |
Secondary
Change in HbA1c (Hemoglobin A1c)
Pre- and post-measurements will be examined for individual change with intranasal oxytocin
Time frame: Baseline to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in HbA1c (Hemoglobin A1c) | -0.05 Percentage | Standard Deviation 0.1857 |
| Placebo Nasal Spray | Change in HbA1c (Hemoglobin A1c) | 0.286 Percentage | Standard Deviation 0.1254 |
Secondary
Change in High Density Lipoproteins (HDL)
Pre- and post-measurements will be examined for individual change with intranasal oxytocin
Time frame: Baseline to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in High Density Lipoproteins (HDL) | 1.000 mg/dL | Standard Deviation 2.8983 |
| Placebo Nasal Spray | Change in High Density Lipoproteins (HDL) | 0.1429 mg/dL | Standard Deviation 3.8408 |
Secondary
Change in Low Density Lipoproteins (LDL)
Pre- and post-measurements will be examined for individual change with intranasal oxytocin
Time frame: Baseline to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in Low Density Lipoproteins (LDL) | -8.727 mg/dL | Standard Deviation 16.224 |
| Placebo Nasal Spray | Change in Low Density Lipoproteins (LDL) | 4.1429 mg/dL | Standard Deviation 11.539 |
Secondary
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.
Time frame: Baseline to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in Montreal Cognitive Assessment (MoCA) | 1.0000 score on a scale | Standard Deviation 1.5954 |
| Placebo Nasal Spray | Change in Montreal Cognitive Assessment (MoCA) | 0.4444 score on a scale | Standard Deviation 1.3333 |
Secondary
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: 1. 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) 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. 3. 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.
Time frame: Baseline to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in Short Physical Performance Battery (SPPB) | 0.5 score on a scale | Standard Deviation 1.446 |
| Placebo Nasal Spray | Change in Short Physical Performance Battery (SPPB) | 0.625 score on a scale | Standard Deviation 1.598 |
Secondary
Change in Total Cholesterol
Pre- and post-measurements will be examined for individual change with intranasal oxytocin
Time frame: Baseline to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in Total Cholesterol | -11.18 mg/dL | Standard Deviation 17.417 |
| Placebo Nasal Spray | Change in Total Cholesterol | -1.143 mg/dL | Standard Deviation 16.056 |
Secondary
Change in Triglycerides
Pre- and post-measurements will be examined for individual change with intranasal oxytocin
Time frame: Baseline to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in Triglycerides | -16.82 mg/dL | Standard Deviation 23.828 |
| Placebo Nasal Spray | Change in Triglycerides | -26.29 mg/dL | Standard Deviation 46.903 |
Secondary
Change in Waist Circumference
Pre- and post-measurements will be examined for individual change with intranasal oxytocin
Time frame: Baseline to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in Waist Circumference | -0.6958 centimeteres | Standard Deviation 4.8662 |
| Placebo Nasal Spray | Change in Waist Circumference | -1.373 centimeteres | Standard Deviation 2.1997 |