The Physiologic Effects of Intranasal Oxytocin on Sarcopenic Obesity (INOSO)

• ClinicalTrials.gov Identifier: NCT03119610
• Recruitment Status: Completed
• First Posted: April 18, 2017
• Results First Posted: October 22, 2020
• Last Update Posted: October 22, 2021
• Sponsor: Sara Espinoza
• Collaborators: 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
• Information provided by (Responsible Party): Sara Espinoza, The University of Texas Health Science Center at San Antonio

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Obesity; Sarcopenic Obesity; Sarcopenia; Aging; Sedentary Lifestyle	Drug: Oxytocin nasal spray; Drug: Placebo nasal spray	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: The Physiologic Effects of Intranasal Oxytocin on Sarcopenic Obesity
• Actual Study Start Date: September 22, 2017
• Actual Primary Completion Date: December 17, 2018
• Actual Study Completion Date: December 17, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Oxytocin nasal spray; Oxytocin (Syntocinon), intranasal, 24IU, 4x a day for 8 weeks, self administered	Drug: Oxytocin nasal spray; Self administered Oxytocin nasal spray q.i.d. for 8 weeks versus placebo (normal saline nasal spray); Other Names: Intranasal oxytocin; Syntocinon nasal spray
Experimental: Placebo nasal spray; Placebo nasal spray, 4x a day for 8 weeks, self administered	Drug: Placebo nasal spray; Self administered Placebo nasal spray q.i.d. for 8 weeks (normal saline nasal spray); Other Name: Saline nasal spray

Outcome Measures

Primary Outcome Measures :

1. Change in Body Weight [ Time Frame: Baseline to 8 weeks ]
   Intranasal oxytocin will promote weight loss and preserve muscle mass

Secondary Outcome Measures :

1. Change in Fat Mass [ Time Frame: 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
2. Change in Body Mass Index [ Time Frame: 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).
3. Change in Glucose Levels Measured Using the Glucose Tolerance Test [ Time Frame: 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
4. Change in Short Physical Performance Battery (SPPB) [ Time Frame: 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.

5. Change in HbA1c (Hemoglobin A1c) [ Time Frame: Baseline to 8 weeks ]
   Pre- and post-measurements will be examined for individual change with intranasal oxytocin
6. Change in Waist Circumference [ Time Frame: Baseline to 8 weeks ]
   Pre- and post-measurements will be examined for individual change with intranasal oxytocin
7. Change in Total Cholesterol [ Time Frame: Baseline to 8 weeks ]
   Pre- and post-measurements will be examined for individual change with intranasal oxytocin
8. Change in Low Density Lipoproteins (LDL) [ Time Frame: Baseline to 8 weeks ]
   Pre- and post-measurements will be examined for individual change with intranasal oxytocin
9. Change in High Density Lipoproteins (HDL) [ Time Frame: Baseline to 8 weeks ]
   Pre- and post-measurements will be examined for individual change with intranasal oxytocin
10. Change in Triglycerides [ Time Frame: Baseline to 8 weeks ]
    Pre- and post-measurements will be examined for individual change with intranasal oxytocin
11. Change in Center for Epidemiologic Studies Scale (CES-D) [ Time Frame: 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.
12. Change in Montreal Cognitive Assessment (MoCA) [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 60 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Texas

Texas Diabetic Institute

San Antonio, Texas, United States, 78207

Sponsors and Collaborators

Sara Espinoza

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

Investigators

• Principal Investigator: Sara Espinoza, MD; The University of Texas Health Science Center, San Antonio

  Study Documents (Full-Text)

Documents provided by Sara Espinoza, The University of Texas Health Science Center at San Antonio:

Study Protocol and Statistical Analysis Plan  [PDF] August 3, 2018

More Information

Publications of Results:

Espinoza SE, Lee JL, Wang CP, Ganapathy V, MacCarthy D, Pascucci C, Musi N, Volpi E. Intranasal Oxytocin Improves Lean Muscle Mass and Lowers LDL Cholesterol in Older Adults with Sarcopenic Obesity: A Pilot Randomized Controlled Trial. J Am Med Dir Assoc. 2021 Sep;22(9):1877-1882.e2. doi: 10.1016/j.jamda.2021.04.015. Epub 2021 May 21.

• Responsible Party: Sara Espinoza, Associate Professor of Medicine, The University of Texas Health Science Center at San Antonio
• ClinicalTrials.gov Identifier: NCT03119610
• Other Study ID Numbers: HSC20160661H
• First Posted: April 18, 2017
• Results First Posted: October 22, 2020
• Last Update Posted: October 22, 2021
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Sarcopenia; Obesity; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Oxytocin; Oxytocics; Reproductive Control Agents; Physiological Effects of Drugs