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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Sedentary Lifestyle; Sarcopenia; Aging; Sarcopenic Obesity
• Intervention / Treatment: Drug: Oxytocin nasal spray; Drug: Placebo nasal spray

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 Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78207
      • Texas Diabetic Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: Saline nasal spray

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sara Espinoza
• Collaborators: The University of Texas Health Science Center, Houston; The University of Texas Medical Branch, Galveston; The University of Texas Health Science Center at San Antonio
• Investigators: Principal Investigator: Sara Espinoza, MD, The University of Texas Health Science Center, San Antonio

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 22, 2017
• Primary Completion (ACTUAL): December 17, 2018
• Study Completion (ACTUAL): December 17, 2019

Study Registration Dates

• First Submitted: March 22, 2017
• First Submitted That Met QC Criteria: April 13, 2017
• First Posted (ACTUAL): April 18, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 22, 2021
• Last Update Submitted That Met QC Criteria: October 1, 2021
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Obesity; Sarcopenia; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: HSC20160661H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No