Clinical trial NCT03119610
Conditions: Obesity Sarcopenic Obesity Sarcopenia Aging Sedentary Lifestyle
Sponsor: Sara Espinoza
Start date: 2017-09-22; Completion date: 2019-12-17
Enrollment: 23 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: Oxytocin (Syntocinon), intranasal, 24IU, 4x a day for 8 weeks, self administered arm 2: Placebo nasal spray, 4x a day for 8 weeks, self administered
Interventions: intervention 1: Oxytocin nasal spray intervention 2: Placebo nasal spray
Intervention descriptions: intervention 1: Self administered Oxytocin nasal spray q.i.d. for 8 weeks versus placebo (normal saline nasal spray) intervention 2: Self administered Placebo nasal spray q.i.d. for 8 weeks (normal saline nasal spray)

Protocol documents:
Prot_SAP_000.pdf: 
OXY-SAR-001 
 
 
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CLINICAL RESEARCH PROTOCOL 
OXY-SAR-001 
 
 
 
THE PHYSIOLOGIC EFFECTS OF  
INTRANASAL OXYTOCIN ON SARCOPENIC OBESITY 
 
 
 
 
 
IND Sponsor: 
Sara Espinoza, MD. Principal Investigator  
Associate Professor, Department of Medicine 
The University of Texas Health Science Center at San Antonio 
(UTHealth San Antonio)  
Barshop Institute for Longevity and Aging Studies 
      7703 Floyd Curl Drive 
      Mail Code 7886 
      San Antonio, Texas 78229-3900 
      (210) 617-5197 
Funding Sponsor: 
NIH/NCATS - Clinical Translational Science Award – Institute for the 
Integration of Medicine and Science 
Study Product: 
Intranasal Oxytocin (Syntocinon; Novartis-Switzerland) 
Protocol Number: 
HSC20160661H (initial approval 03/24/2017) 
IND Number: 
IND# 132460-0007  
NCT#: 
NCT03119610 
Clinical Sites: 
 
University of Texas Health Science 
Center at Houston (UTHealth)  
 
Principal Investigator:   
   Jessica Lee, MD 
 
 
University of Texas Medical Branch 
(UTMB), Galveston 
 
Principal Investigator:   
  Elena Volpi, MD 
 
 
University of Texas Health Science 
Center at San Antonio (UTHSCSA) 
 
Principal Investigator:    
  Sara Espinoza, MD    
Coordinating Center 
 
Clinical Trials Express 
6410 Fannin Street 
UTPB1100.34 
Houston, TX 77030 
 
 


OXY-SAR-001 
 
 
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TABLE OF CONTENTS 
 
 
STUDY SUMMARY………………………………………………………………………..…... 
1 
1 
INTRODUCTION………………………………………………………………………... 
2 
 
1.1 BACKGROUND……………………………………………………………………… 
2 
 
1.2 SIGNIFICANCE……………………………………………………………………... 
2 
 
1.3 PRELIMINARY DATA………………………………………………………………... 
3 
 
1.4 INVESTIGATIONAL AGENT………………………………………………………….. 
3 
 
1.5 DOSE RATIONALE AND RISK/BENEFITS………………………………………….... 
3 
2 
STUDY OBJECTIVE……………………………………………………………………. 
3 
3 
STUDY DESIGN………………………………………………………………………… 
3 
 
3.1 SUBJECTS……………………………………………..……………………….….. 
3 
 
3.2 GENERAL DESIGN……………………………………………………………..…... 
4 
 
3.3 STUDY ENDPOINTS……………………………………………...………………... 
4 
 
3.4 POTENTIAL RISKS TO SUBJECT SAFETY…………………………………………...
4 
4 
SUBJECT SELECTION AND WITHDRAWAL………………………………………. 
5 
 
4.1 INCLUSION CRITERIA…………………………………………………………….… 
5 
 
4.2 EXCLUSION CRITERIA……………………………………………………………… 
6 
 
4.3 RECRUITMENT AND SCREENING…………………………………………….…….. 
6 
 
4.4 EARLY WITHDRAWAL…………………………………………………….……...... 
6 
5 
STUDY DRUG………………………………………………………………………....... 
7 
 
5.1 DESCRIPTION…………………………………………………………………….... 
7 
 
5.2 TREATMENT REGIMEN…………………………………………………………..... 
7 
 
5.3 PREPARATION AND ADMINISTRATION OF STUDY DRUG………………………….. 
7 
 
5.4 PRIOR AND CONCOMITANT THERAPY………………………………………….…. 
8 
 
5.5 PACKAGING………………………………………………………………………… 
8 
 
5.6 RECEIPT, STORAGE, AND HANDLING OF STUDY DRUG………………………….. 
8 
6 
STUDY PROCEDURES………………………………………………………………... 
9 
 
6.1 VISIT 1……………………………………………………………………….……. 
9 
 
6.2 VISIT 2……………………………………………………………………...…..…. 
9 
 
6.3 VISIT 3  / RANDOMIZATION..………..……………………………………….…. 
10 
 
6.4 VISIT 4………………………………………………………………………….…. 
10 


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6.5 VISIT 5………………………………………………………………………….…. 
11 
 
6.6 VISIT 6………………………………………………………………………….…. 
11 
 
6.7 VISIT 7………………………………………………………………………….…. 
11 
 
6.8 VISIT 8………………………………………………………………………….…. 
11 
7 
STATISTICAL PLAN…………………………………………………………………... 
12 
 
7.1 SAMPLE SIZE DETERMINATION………………………………………………….... 
12 
 
7.2 STATISTICAL METHODS…………………………………………………….…….. 
13 
8 
SAFETY AND ADVERSE EVENTS…………………………………………….….…. 
13 
 
8.1 DEFINITIONS…………………………………………………………………….… 
13 
 
8.2 RECORDING AND REPORTING OF ADVERSE EVENTS…………………………..... 
14 
 
8.3 RECORDING AND REPORTING OF SAE/UPIRSO………………………..………. 
15 
 
8.4 MEDICAL MONITORING……………………………………………………………. 
16 
 
8.5 UNBLINDING……………………………………………………………………….. 
17 
 
8.6 STOPPING RULES…………………………………………………………………. 
17 
9 
DATA HANDLING AND RECORD KEEPING……………………………………...... 
18 
 
9.1 CONFIDENTIALITY…………………………………………………………………. 
18 
 
9.2 SOURCE DOCUMENTS…………………………………………………………….. 
18 
 
9.3 DATA MANAGEMENT……………………………………………………………… 
18 
 
9.4 RECORDS RETENTION……………………………………………………….…... 
18 
10 
STUDY MONITORING, AUDITING, AND INSPECTING………………………….... 
19 
 
10.1 STUDY MONITORING PLAN………………………………………………………… 
19 
 
10.2 AUDITING AND INSPECTING……………………………………………………….. 
19 
11 
ETHICAL CONSIDERATIONS…………………………………………………….…... 
20 
12 
STUDY FINANCES................................................................................................. 
20 
 
12.1 FUNDING SOURCE…………………………………………………….…………... 
20 
 
12.2 CONFLICT OF INTEREST…………………………………………………………… 
20 
 
12.3 SUBJECT STIPEND OR PAYMENTS………………………………………………… 
20 
13 
REFERENCES……………………………………………………………….………….. 
21 
14 
ATTACHMENTS………………………………………………………………………… 
22 
 
A. PLACEHOLDER FOR SAMPLE CONSENT FORM…………………………………… 
23 
 
B. PLACEHOLDER FOR EVENT SCHEDULE…………………………………………… 
24 
 
C. PLACEHOLDER FOR DRUG SUPPLIER (VICTORIA APOTHEKE ZURICH/NOVARTIS). 
25 
 
D. PLACEHOLDER FOR QUESTIONNAIRES AND INSTRUMENTS……………………… 
26 
 
E. PLACEHOLDER FOR SUMMARY OF PROTOCOL REVISIONS 
27-29 
 
 
 


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List of Abbreviations 
 
 
 
 
 
OGTT – Oral Glucose Tolerance Test 
SPPB – Short Physical Performance Battery 
SIADH – Syndrome of Inappropriate Antidiuretic Hormone Secretion 
TUG – Timed Up and Go 
Mini-Cog – Mini-Cog test - Screening for Cognitive Impairment in Older Adults 
MoCA – Montreal Cognitive Assessment 
GDS – Geriatric Depression Scale 
CES-D – Centers for Epidemiologic Studies Depression Scale 


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CONFIDENTIAL 
       Study Summary 
Title 
The Physiologic Effects of Intranasal Oxytocin on Sarcopenic Obesity 
Protocol Number 
OXY-SAR-001 
Phase 
II 
Methodology 
Eligible subjects self-administer 24 IU intranasal oxytocin q.i.d. 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. 
Study Duration 
12 weeks ± 1 week 
Study Center(s) 
UTHSCSA, UTHealth (Houston), UTMB (Galveston) 
Objective 
1) To assess the effect of intranasal oxytocin administration on body weight, 
adiposity, muscle mass, and glucose tolerance in older adults.  
2) To assess the effect of intranasal oxytocin on physical function and 
physiologic parameters of insulin signaling, inflammation, and muscle 
regeneration in older adults.  
Number of Subjects 
36 completers (3 sites, up to 15 at each site, allowing for attrition) 
Inclusion Criteria 
Age ≥60 years 
BMI 30.0-43.0 kg/m2 
Sedentary (≤2 strenuous exercise/week) 
Gait speed < 1 meter/second 
Exclusion Criteria 
1) Diabetes with Hemoglobin A1c (HbA1c) ≥ 6.5 and/or taking medications 
known to effect glucose homeostasis 
2) Significant heart disease (history of MI within the last year or New York 
Heart Classification grade III-IV) 
3) Poorly controlled hypertension (SBP > 170 or DBP >95 mm/Hg) 
4) Anemia (Hematocrit <34%) 
5) Renal Disease (glomerular filtration rate [GFR] < 30 mL/min, abnormal 
serum sodium levels, ≥ 5 white blood cells or ≥ 5 red blood cells on 
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) 
6) Liver Disease (AST/ALT/AlkPhos > 2 x upper limit of normal) 
7) Use of systemic steroid, androgens, or anti-coagulants 
8) Active/unstable conditions: inflammatory, thyroid, autoimmune, 
gastrointestinal (GI), hematologic, or neoplastic disorders (Exclude 
subjects with clinical lab values outside the normal range (other than as 
specified above)) 
9) Individuals with underlying seizure disorder or underlying neurologic 
disorder that increases seizure risk 
10) Cognitive impairment (MiniCog <3), unstable mental illness or GDS > 7, 
substance abuse, or history of eating disorder 
Study Product, Dose, 
Route, Regimen 
Intranasal Oxytocin 24 IU self-administered q.i.d. (3 puffs each nostril 4x/day) 
for 8 weeks 
Statistical Methodology 
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 
 
 


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1.4. Preliminary Data 
Recent work in mice showed that short-term systemic oxytocin delivery restores muscle regeneration in old mice 
by improving aged muscle stem cell function 4. This work also demonstrated that oxytocin acts directly on muscle 
stem cells (in vitro and in vivo) and that the pro-myogenic effects of oxytocin are mediated by MAPK/ERK 
signaling. The effect of oxytocin on skeletal muscle in humans has not yet been studied to our knowledge.    
1.5. Investigational Agent 
Intranasal oxytocin was marketed in the U.S. beginning in 1957 and used in the 1960’s in the postpartum period 
for milk let-down. It was taken off the market in 1995 in the U.S., but it is still available in Europe. There are 
several clinical trials now listed on clinicaltrials.gov studying the use of intranasal oxytocin for autism, dementia, 
and other psychological and developmental conditions.   
1.6. Dose Rationale and Risk/Benefits 
With assistance from the College of Pharmacy of University of Texas at Austin, we performed a literature review 
of the safety and side effect profile of intranasal oxytocin. To summarize, the studies reviewed that studied 
lactation did not have any significant adverse events or complications related to the use of intranasal oxytocin. 
The side effects noted with intranasal oxytocin were rare instances of headache, nausea, and allergic dermatitis 
(between 1/1000 and 1/10,000 occurrences, and occasional abnormal uterine contractions (between 1/100 and 
1/1000 occurrences). In our study we expect fewer uterine contraction occurrences since none of the women 
enrolled will be postpartum and all will be post-menopausal. In studies that examined the use of intranasal 
oxytocin for conditions other than lactation, a recent article on this subject was also recently published 22. This 
article reviewed 38 trials and 3 case reports of both men and women. Mild adverse events were reported by 279 
out of 1529 subjects and consisted of light headedness, vertigo, drowsiness, sleepiness, dry mouth, nasal 
irritation, runny nose, abdominal pain, anxiety, euphoria, increased energy, relaxation, calm sensation, and 
headache.  
 
In this study we propose to use intranasal oxytocin to examine its physiologic and metabolic effects. We propose 
to use the same dose as recently reported by Zhang et al. 2.  In this recently conducted study, 24 subjects were 
randomized to intranasal oxytocin (24 IU QID) or placebo for a period of 8 weeks.  They demonstrated that there 
was no cardiovascular, hepatic or renal dysfunction related to the use of intranasal oxytocin. In fact, they noted 
improved hepatic function in the oxytocin group.  Based on the review of the literature and recent published 
studies indicating the safe use of intranasal oxytocin, we feel that intranasal oxytocin can be safely administered 
in a research study to examine its physiologic effects such as we propose.  
 
2. Study Objective 
a) To assess the effect of intranasal oxytocin administration on body weight, adiposity, muscle mass, and 
glucose tolerance in older adults. 
b) To assess the effect of intranasal oxytocin on physical function and physiologic parameters of insulin 
signaling, inflammation, and muscle regeneration in older adults.  
 
3. Study Design 
3.1. Subjects 
Population: 36 obese (BMI 30.0-43.0 kg/m2) sarcopenic (see below) subjects aged ≥60 years will be 
randomized to either intra-nasal oxytocin or placebo (saline) for 8 weeks.  Oxytocin (Syntocinon; Novartis-
Switzerland via  


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Victoria Apotheke Zürich) will be dosed at 24 IU four times a day (before each meal and at bedtime)2. 
Additional inclusion criteria (as shown 
in Table 1), are stable body weight, 
sedentary lifestyle (within the last 6 
months), and sarcopenic obesity.  
 
Sarcopenic obesity is defined using a 
modified consensus criteria of gait 
speed <1 meter/second 12. Exclusion 
criteria are shown in Table 1.  Muscle 
mass will be measured as an outcome 
variable, however, it will not be used as 
a basis for inclusion. 
 
3.2. General Design 
 
Randomized, placebo controlled Phase 
II pilot study to be conducted at 3 
clinical sites: UTHealth San Antonio, 
UTHealth in Houston, and UTMB in 
Galveston. 
 
3.3. Study Endpoints 
 
Primary outcomes: Change in weight, adiposity,  
muscle mass, and physical function (gait speed, strength, SPPB). This is a pilot study which will examine 
change in these outcomes prior to and after treatment.  
 
Secondary outcomes:  Change in glucose 
tolerance as measured by OGTT, measures of 
systemic inflammation (TNF-α, C-reactive protein, 
IL-6, adiponectin), muscle inflammation (IL-1β, IL-6, 
MCP-1, TNF-α mRNA), and muscle stem cell 
number and proliferative capacity. This is a pilot 
study which will examine change in these outcomes 
prior to and after treatment. 
 
3.4. Potential Risks to Subject Safety 
Drug Administration. 
 
Rare: (observed in <1% of subjects) 
• 
Nausea 
• 
Allergic dermatitis 
• 
Occasional abnormal uterine contractions (unlikely in post-menopausal subjects) 
• 
Hyponatremia and or fluid imbalance 
 
Mild: (observed in 10-20% of subjects) 
able 1. Inclusion and exclusion criteria 
Inclusion Criteria 
Age ≥60 years 
BMI 30.0-43.0 kg/m2 with stable body weight (±2%) in past 3 months 
Sedentary (≤2 strenuous exercise/week) 
Gait speed < 1 meter/second 
Exclusion Criteria 
Diabetes  with HbA1c ≥ 6.5 and/or taking medications known to effect glucose 
homeostasis, Significant heart disease (history of MI within the last year or New 
York Heart Classification grade III-IV) Poorly controlled hypertension (SBP >170 or 
DBP >95 mmHg), Anemia, Renal Disease (as specified in Section 4 below), or Liver 
Disease 
Use of systemic steroids/androgens or anticoagulants 
Active/unstable inflammatory, thyroid, autoimmune, gastrointestinal (GI), 
hematologic or neoplastic disorders (Exclude subjects with clinical lab values 
outside the normal range (other than as specified above)) 
Cognitive impairment (Mini-Cog <3), unstable mental illness or GDS > 7, 
substance abuse, or history of eating disorder 
Table 2. Outcome variables 
Primary Outcome 
Secondary Outcome 
Adiposity (BMI, DEXA) 
Glucose tolerance (OGTT) 
Muscle mass (DEXA, MRI, 
muscle fiber CSA) 
Systemic and muscle 
inflammation 
Physical function (gait speed, 
muscle strength, balance) 
Muscle stem cell number and 
proliferative capacity 


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• 
Light-headedness 
• 
Vertigo 
• 
Drowsiness 
• 
Sleepiness 
• 
Dry mouth 
• 
Nasal irritation 
• 
Runny nose 
• 
Abdominal pain 
• 
Anxiety 
• 
Euphoria 
• 
Increased energy 
• 
Relaxation 
• 
Calm sensation 
• 
Headache 
Blood withdrawal.   
All studies involve the withdrawal of blood. Any subject who has donated blood in the previous two months 
will not be studied. The subjects will be instructed not to donate blood for two months after the study.  Any 
subject with a hematocrit of < 34% will not be studied.  Blood will be collected for safety and for research 
purposes at screening and study visits. Upon subject-reported history of any condition (known or suspected) 
that would be exclusionary, investigator may choose to order appropriate additional clinical labs to ensure 
eligibility.  
IV lines.   
Catheters will be placed in an antecubital vein or a hand vein for the OGTT.  Local hematomas occur in 
about 1% of catheterizations.  Infection is possible (<1%), but we have not experienced this complication.   
Muscle biopsy.   
At the time of biopsy, subjects may feel pain, discomfort, or pressure (variably described by different 
subjects) for about 5-10 seconds.  Pain or discomfort ceases as soon as the cannula is withdrawn.  Local 
hematomas occur in <2% of subjects.  One patient experienced a moderately painful hematoma that 
resolved within 2 weeks (0.1%).  About 1 in 50 subjects report non-clinically evident numbness or altered 
sensation at the biopsy site, which is transient.  
 
There is the possibility that a future biopsy may not be done at the discretion of the PI in case the subject 
did not tolerate well a prior biopsy. 
Radiation exposure. 
Subjects will be exposed to a small amount of radioactivity during DEXA. 
 
4. Subject Selection and Withdrawal 
4.1. Inclusion Criteria 
• 
Both genders. 
• 
Age ≥ 60 years.  
• 
All ethnic groups. 
• 
BMI 30.0-43.0 kg/m2 with stable body weight (±2%) in past 3 months. 
• 
Sedentary (≤2 sessions of strenuous exercise/week) 


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• 
Gait speed < 1 meter/second 
• 
Labs: HCT ≥34%,  GFR ≥ 30 mL/min, liver enzymes (AST < 2 x upper limit of normal, ALT < 2 x upper 
limit of normal, alkaline phosphatase < 2 X upper limit of normal), normal electrolytes,  urinalysis with < 
5 red blood cells (RBCs) and < 5 white blood cells (WBCs) , and normal PT and PTT. If additional labs 
are drawn to ensure eligibility, inclusion requires lab results fall within the normal range per local lab. 
Note: Some sites may draw additional clinical labs per local standard operating procedure, which are not 
collected as research data for this study. 
 
 
4.2. Exclusion Criteria 
• 
Diabetes  with HbA1c ≥ 6.5 and/or taking medications known to effect glucose homeostasis  
• 
Significant heart disease (history of MI within the last year or New York Heart Classification grade III-IV) 
• 
Poorly controlled hypertension (SBP >170 or DBP >95 mmHg) 
• 
Anemia (HCT <34%) 
• 
Renal Disease ( GFR < 30 mL/min), abnormal serum sodium levels, urinalysis with ≥ 5 RBCs or ≥ 5 
WBCs, 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 or abnormal liver enzymes (AST > 2 x upper limit of normal, ALT > 2 x upper limit of 
normal, alkaline phosphatase > 2 X upper limit of normal) 
• 
Use of systemic steroids or androgens 
• 
Individuals with underlying seizure disorder or underlying neurologic disorder that increases seizure risk 
• 
Current treatment with anticoagulants (i.e. warfarin). Aspirin (up to 325 mg) and clopidogrel will be 
permitted if these can be held for seven days prior to the biopsies. 
• 
Active/unstable conditions: inflammatory, thyroid, autoimmune, gastrointestinal (GI), hematologic, or 
neoplastic disorders. Exclude subjects with clinical lab values outside the normal range (other than as 
specified above). 
• 
Cognitive impairment (Mini-Cog <3) 
• 
Unstable mental illness (GDS > 7) 
• 
Substance abuse 
• 
History of eating disorder 
• 
Subject is considered unsuitable for the study in the opinion of the investigator for any other reason 
4.3. Subject Recruitment and Screening 
Subjects will be recruited through the institutional volunteer registries and advertisement (newspaper, flyers, 
etc.). All study visits will be performed in the Clinical Research Centers (CRCs) of UTHealth San Antonio, UHS, 
UTMB and UTHealth-Houston. At some sites, subjects will call-in to an advertised number and will be pre-
screened using an institutionally-approved process. Callers then provide permission for a research team 
member to follow up with phone screening using an IRB-approved form (sample contained in Attachment D 
section) and staff will schedule the screening visit if the potential subject agrees If potentially eligible following 
the telephone screening process, an in-person screening visit will be conducted.   
 
Screening evaluation will follow informed consent at Visit 1 and will include: medical history, physical 
examination (including anthropometric measurements), Mini-Cog, and screening blood tests (complete blood 
count, chemistry, lipid profile, hemoglobin A1c, coagulation tests, urinalysis). 
 
 


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4.4. Early Withdrawal of Subjects 
4.4.1. When and How to Withdraw Subjects 
Subjects have the right to withdraw fully or partially from the study at any time and for any reason without 
prejudice to his or her future medical care by the physician or at the institution. 
 
Withdrawal of full consent for a study means that the subject does not wish to receive further investigational 
treatment and does not wish to or is unable to continue further study participation including any follow-up in 
person, by phone, through third parties including relatives or friends, via discussion with other treating 
physicians, and by use of medical records; subject data up to withdrawal of full consent will be included in the 
analysis of the study. Any subject may withdraw full consent to participate in the study at any time during the 
study. The Investigator or sub-investigator will discuss with the subject appropriate procedures for withdrawal 
from the study. 
 
Final Study Visit for Withdrawn Subjects 
At the time of receiving notification of intended withdrawal, researchers will ask subject to complete a final 
visit. The informed consent document advises subjects to discuss withdrawal decision with the principal 
investigator. This visit includes a repeat history and physical examination, weight, functional testing, 
Bioimpedance (UTMB site only), DEXA, questionnaires, and laboratory tests (safety labs, inflammatory 
markers). Subjects may choose to complete all or part of the final study visit. 
 
4.4.2. Data Collection and Follow-up for Withdrawn Subjects 
If subjects are withdrawn prematurely from the study, appropriately designated research staff will make efforts 
to collect at least survival data throughout the protocol defined follow-up period for that subject.  
 
Investigator will consult with Study Statistician with regard to any incomplete data set as compared to the full 
data set that fully supports the analysis.  If a subject withdraws consent to participate in the study, attempts will 
be made to obtain permission to record survival data up to the protocol-described end of subject follow-up period.  
 
Investigator and designated research staff make it a high priority to obtain survival data on all subjects lost to 
follow up. Lost to follow up will be defined as a subject missing 2 or more consecutive visits, not answering or 
responding to 3 follow up phone calls to subject or emergency contacts, or returned receipt of 1 certified letter.  
5. Study Drug 
5.1. Description 
See Attachment D. Victoria Apotheke Zurich: Syntocinon, Drug information 
5.2. Treatment Regimen 
Subjects are instructed to administer 3 sprays per nostril (24 IU) 4 times a day for 8 weeks (56 days). 
Method for Assigning Subjects to Treatment Groups 
The randomization key will be designed by a biostatistician or sponsor’s designee not directly engaged in the 
research and key will be provided to the research pharmacy for coding study drug. After the key is created, the 
research pharmacy will keep the randomization key in case unblinding is necessary at any point during the 


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study.  
 
Subject ID numbers will be generated in REDCap based on the data management design. The Study 
Coordinator at each site stores the Enrollment key, which is kept in a locked cabinet or on a secure server with 
limited access.  
 
Study staff maintains data records, and specimens, in a de-identified manner using only the unique Subject 
ID/Randomization number. Only the secure source documents may contain subject identifiers (name, DOB, 
SSN, etc.) 
5.3. Preparation and Administration of Study Drug 
Intranasal Administration Protocol. 
To prime a new bottle: 
• 
Hold the bottle upright and away from you, then pump it several times until you see a faint spray.  
• 
Do not prime the pump again before each daily use.  
 
To use the nose spray: 
• 
Before using the spray, blow your nose gently to clear the nostrils.  
• 
Keeping your head in an upright position, carefully place the nozzle into one nostril, aiming straight back 
toward the base of the skull. Do not aim the nozzle straight up toward the top of the head. 
• 
Press the pump toward the bottle and spray as directed.  
• 
Do not inhale while spraying. Breathe or sniff gently through the nose after spraying and do not blow 
nose again for at least 30 minutes. 
• 
To keep the nosepiece clean, wipe it with a clean tissue and replace the dust cap after use.  
 
Subject Compliance Monitoring 
A drug diary will be provided to all subjects at the time of drug dispensing at Visit 3 (or Visit 4 if optional MRI is 
completed). Subjects will be instructed to log their use of the study drug daily and bring the drug diary to each 
visit. 
5.4. Prior and Concomitant Therapy 
Exclusionary medications:  
Drugs that affect glucose homeostasis, systemic corticosteroids, androgens.  
Treatment with anticoagulants (warfarin). Aspirin (up to 325 mg) and clopidogrel will be permitted if these can 
be held for seven days prior to the biopsies. 
5.5. Packaging    
 
Nature and Contents of the Container 
Victoria Apotheke Zurich will supply blinded product and placebo, package for refrigerated shipping, and manage 
customs and importation documents. 
5.6. Receipt, Storage and Handling of Study Drug 
Local site Research Pharmacy will be responsible for receipt, inventory, storage, and destruction of Study Drug. 


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Receipt of Drug Supplies 
Any damaged or unusable study drug in a given shipment will be documented by the receiving Pharmacy.  The 
Research Pharmacist will notify the IND Sponsor of any damaged study drug. 
 
Special instructions upon receipt 
Open package, review and compare to shipping documents, log inventory counts and refrigerate. 
Storage 
Nasal spray: Store in a refrigerator (2–8°C or 35.6°F–46.4F). 
Shelf life: After opening the bottle, store the nasal spray at room temperature (15–25°C) and use within 1 month. 
Dispensing of Study Drug 
Designated staff from the site Research Pharmacy maintains the Drug Accountability Logs to track how, when 
and to whom the investigational drug was prescribed, dispensed and assigned to subjects. Study clinical staff 
will keep drug administration records regarding drug that is damaged or wasted.   
 
Routine study drug administration and reconciliation will be performed based on clinical site policy and standard 
operating procedures. 
Return or Destruction of Study Drug 
The procedures for final reconciliation of the site’s drug supply at the end of the study will be in accordance with 
local site Pharmacy standard operating procedures. There are no special precautions cited for disposal of 
Intranasal Oxytocin. 
 
6. Study Procedures 
Study visits. All studies will be performed in the Clinical Research Center at the designated site(s). 
6.1. Visit 1 (Consent, Screening for Eligibility, and Baseline Testing – Day 0) 
Subjects present in fasting state to the site CRC at appointed time for informed consent processing, medical 
history and physical exam to assess inclusion and exclusion criteria, including measurements of weight, gait 
speed, waist circumference, hematology, coagulation studies, chemistry with liver function, lipid panel, urinalysis, 
and serum and urine osmolality. A 2-hour OGTT will be performed to assess glucose tolerance. . Screening mental 
status assessments (Mini-Cog and depression scale) will be performed to ensure valid consenting process. If 
subjects meet initial eligibility criteria based on walking speed and history & physical examination.  Individuals 
meeting eligibility will proceed to a 2-hour OGTT. During the 2-hour OGTT,  baseline testing will be performed, 
including labs, food recall and appetite assessments and psychometrics. After the 2-hour OGTT, the participant 
will be given a meal or substantial snack (per local clinical research unit) and continue with the functional testing. 
A screening window of 30 days is allowed so that all laboratory and test results can be returned and reviewed. 
Estimated length of this visit is 6 hours. 
• 
Vital signs will be assessed for blood pressure, heart rate, respiratory rate and temperature 
• 
Walking speed will be assessed at usual speed over a 15-foot course 
• 
Waist circumference will be measured in inches and converted to centimeters.  
• 
Weight in pounds will be measured or calculated in kilograms and used in BMI calculation. 
• 
History & physical examination, targeted to the inclusion & exclusion criteria will be performed to 
determine study eligibility.   


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• 
Laboratory tests: CBC, CMP with liver function, Hemoglobin A1c, coagulation test (PT/INR, PTT), 
urinalysis, serum osmolality, urine osmolality, lipid panel. Order additional labs, if necessary, based on 
pertinent medical history. 
• 
Psychometrics: Mini-Cog scoring < 3 will not be studied; Geriatric Depression Scale (GDS) scoring > 7 
will not be studied and warrants follow up assessment with mental health professional 
• 
Electrocardiogram (ECG): ECG with definitive evidence of prior myocardial infarction will not be studied 
• 
2-hour OGTT: Baseline (fasting) samples for determination of glucose and insulin concentrations will be 
drawn at -30, and -15 minutes (these basal values are averaged). At time zero, each subject will ingest 
75 g of glucose. Glucose and insulin are determined every 30 minutes for 2 hours following glucose 
ingestion. The Matsuda index of insulin sensitivity will be calculated from the OGTT results, as described 
13.   
• 
Food recall and appetite assessments: A 24-hour food recall, 3-day food diary, and appetite will be 
assessed using standardized questionnaires14, 15. 
• 
Psychometrics: The Montreal Cognitive Assessment (MOCA) and The Centers for Epidemiologic Studies 
Depression Scale (CES-D) will be administered for baseline measurement. 
• 
Functional Testing: Timed Up and Go (TUG) and Short Performance Physical Performance Battery 
(SPPB, modified) will be measured using standardized methods 23, 24. Grip strength will be assessed 
using handheld digital dynamometer. 
 
6.2. Visit 2: Optional MRI (within 7 days after V1) 
MRI (optional): Image of the abdomen and dominant lower extremity will be done if funding is available to examine 
the effect of oxytocin on abdominal visceral fat and thigh muscle volume as described 25. If participant has a 
pacemaker or any other reason that would preclude obtaining an MRI, this procedure can be omitted at the 
discretion of the PI. 
 
6.3. Visit 3 – Physiological measures and Randomization  (within 7-14 days after V2) 
 
Subjects present to the site CRC in fasting state to assess body composition, bioimpedance, calorimetry, 
muscle biopsy, and systemic inflammation. An intravenous (IV) line is placed for access during muscle biopsy. 
• 
Vitals signs, weight and BMI 
• 
DEXA: Whole body dual-energy X-ray absorptiometry is performed to measure lean and fat body mass 
• 
Bioimpedance: Measures weight, body fat percentage, and body mass index (BMI). The BF-350 is an 
FDA-cleared body composition monitor is an affordable solution for mainstream healthcare and fitness 
providers. Bioimpedance will be performed at UTMB Galveston site only. 
• 
Calorimetry: Indirect calorimetry is performed in fasting state at rest for 30 minutes. Calorimetry will not 
be performed at UT Houston due to unavailability of required equipment. Since this is not a major outcome 
of the study, this does not significantly affect the scientific integrity of the study. 
• 
Muscle Biopsy: Vastus lateralis muscle needle biopsy will be performed to assess muscle fiber type, 
satellite cells, and inflammatory markers.  
• 
Laboratory and blood draw: Systemic inflammatory markers (see Analyses) 


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• 
Adverse event review questionnaire will be completed. 
 
Analyses.  
Muscle:  
A biopsy of the vastus lateralis muscle will be performed as described using aseptic technique 17. The following 
measurements will be performed: 
• 
Muscle fiber cross sectional area (CSA) 18 
• 
Satellite (stem) cell number and proliferative capacity 19, 20 
• 
Inflammatory genes / proteins.  Measurements of NFκB and MAPK signaling, two key mediators of the 
inflammation state, will be conducted as described 21. We will also assess cellular inflammation by 
measuring the levels of the mRNA transcripts for IL-1β, IL-6, MCP-1, and TNFα mRNA in skeletal muscle 
before and after oxytocin treatment 21.   
Blood/plasma:  
• 
Systemic inflammation - measuring plasma concentration of TNF-α, C-reactive protein, IL-6, and 
adiponectin, using commercially available ELISA kits.  
 
Randomization. Subject will be randomized to study drug or placebo and dispensing occurs at the end of V3.  
 
6.4. Visit 4. Safety Labs (+1 week since start of study drug, within ±3-day window) and drug tolerability 
Subjects present in fasting state to the site CRC to assess:  
• 
Vital signs, weight, BMI, waist circumference 
• 
Safety labs: Chemistry (including serum sodium), liver function, urine osmolality and serum osmolality 
• 
Food recall: repeat 24-hour food recall, 3-day food diary and appetite assessments (same as Visit 1) 
• 
Drug tolerability: subjects will be assessed for drug tolerability, including any side effects or adverse effects. 
Special attention will be made for signs and symptoms suggestive of hyponatremia including lethargy, 
muscle spasms, seizures, confusion/delirium, nausea and vomiting 
 
6.5. Visit 5 Safety Labs (+4 weeks of drug administration, within ±7-day window) and drug tolerability 
Subjects present in fasting state to the site CRC to assess:  
• 
Vital signs, weight, BMI, waist circumference 
• 
Drug compliance and tolerability, AE review 
• 
Psychometrics: repeat MOCA and CES-D 
• 
Food recall: same as Visit 1 
• 
Safety labs: chemistry with liver function, urine osmolality and serum osmolality 
 
6.6. Visit 6; Post treatment measurements (6-7.5 weeks on treatment)  
Subjects present in fasting state to the site CRC to assess:  
• 
Vital signs, weight, BMI, waist circumference 
• 
Laboratory: CBC, chemistry with liver function, lipid panel, urine and serum osmolality, hemoglobin A1c, 
coagulation tests (PT/INR, PTT)  
• 
Functional testing: Gait speed, grip strength, modified SPPB, TUG 
• 
Food recall: same as Visit 1 


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• 
2-hour OGTT 
• 
Drug compliance and tolerability, AE review  
6.7. Visit 7: Optional MRI (if done at V2) – (7-7.5 weeks on treatment)   
MRI (optional): Image of the abdomen and dominant lower extremity will be done if completed at Visit 2. If 
participant has a pacemaker or any other reason that would preclude obtaining an MRI, this procedure can be 
omitted at the discretion of the PI. 
6.8. Visit 8: Post treatment measurements (7.5-8 weeks of treatment) 
Subjects present in fasting state to the site CRC to assess:  
• 
Vitals signs, weight, BMI, waist circumference  
• 
MOCA, CES-D 
• 
DEXA body composition, Bioimpedance (UTMB Galveston only) and Calorimetry 
• 
Muscle biopsy (satellite cell, fiber type, fat infiltration, inflammation, gene expression) 
• 
Blood draw: Systemic inflammation 
• 
Drug tolerability, compliance, and AE review 
 
 
See Summary of Visits Table on next page. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Summary of Visits Table 
 


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Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
  
Screen 
Day 0 
(fasting) 
 MRI 
+ 7d 
 V2     
+7-14d 
(fasting) 
1 week on 
treatment 
(fasting) 
4 weeks 
on  
treatment 
(fasting) 
6-7.5 
weeks on 
treatment 
(fasting) 
MRI  
7-7.5 
weeks on 
treatment    
7.5-8 
weeks on 
treatment 
(fasting) 
Medical history and 
physical examination, 
ECG 
X 
  
  
  
  
  
  
  
Vital signs, Weight, BMI  
X 
  
X  
X  
 X 
X 
X 
Waist circumference 
X 
 
 
X 
X 
X 
 
X 
Mini-Cog 
X 
  
  
  
  
  
  
  
Montreal Cognitive 
Assessment (MOCA) 
X 
 
 
 
X 
 
 
X 
Geriatric depression scale 
(GDS) 
X 
 
 
 
 
 
 
 
Centers for Epidemiologic 
Studies Depression Scale 
(CES-D) 
X 
 
 
 
X 
 
 
X 
Gait speed, 15-foot course 
X 
  
  
  
  
 X 
 
  
Electrocardiogram 
X 
 
 
 
 
 
 
 
**CBC, HgbA1c, and 
Coagulation testing 
(PT/INR, PTT) 
X 
  
  
  
  
 X 
 
  
**Chemistry with liver    
function, serum osmolality 
(other safety labs if 
clinically indicated by 
history) 
X 
  
  
 X 
X 
X 
 
  
**Lipid Panel 
X 
 
 
 
 
X 
 
 
Urinalysis 
X 
  
  
  
  
  
  
  
Urine osmolality 
X 
  
  
 X 
X  
X 
 
  
OGTT, 2-hour 
X 
 
 
 
 
X 
 
 
Body composition (DEXA) 
  
 
X 
 
X 
Bioimpedance (UTMB 
only) 
  
 
X 
 
X 
Calorimetry 
  
 
X 
 
 
 
 
X 
Randomization* 
 
 
X 
 
 
 
 
 
Body composition    (MRI) 
- optional 
  
 X 
  
 
  
  
 X 
 
Functional tests: mSPPB, 
TUG, grip strength 
X 
 
 
 
 
X 
 
 
24-hour food recall, 3-day 
food diary, appetite 
X 
 
 
X 
X 
X 
 
 
Muscle biopsy 
 
 
X 
 
 
 
 
X 
Systemic inflammation 
 
 
X 
 
 
 
 
X 
Drug tolerability, 
compliance,AE review 
  
  
AE 
review 
only  
X  
X 
X 
 
X 
 
* After Visit 4, participants may receive periodic phone calls by study staff between study visits to assess any 
symptoms and encourage adherence to study drug.  
** Any marginally abnormal lab findings may be repeated if clinically indicated to ensure initial or continued 
eligibility. 


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7. Statistical Plan 
7.1. Sample Size Determination  
Our power and sample size estimation is based on findings from an 8-week study of intranasal oxytocin in 24 
adults, which found a greater reduction in body weight and BMI with oxytocin. Based on their findings, our 
proposed study (12 completers each site for 36 completers total, 18 completers in each arm) is expected to 
have 96.4% power to detect the oxytocin effect if the standard deviation (SD) associated with weight loss is 
6.0 kg in the oxytocin group and 1.5 kg in the control group. For a more conservative estimate assuming a SD 
of 6.0 in both the oxytocin and control groups, our study would have 78.2% power. For both these power 
analyses, we assume type 1 error of P=0.05.  
 
7.2. Statistical Methods 
Analytical Approach. 
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. Normal transformed score of an outcome will be used 
in the analyses when appropriate.  
 
8. Safety and Adverse Events 
8.1. Definitions 
Adverse Event (AE) 
In general, AE is used very broadly and encompasses physical and psychological harms and includes:   
 
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for 
example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with 
the subject’s participation in the research, whether or not it is considered related to the subject’s participation 
in the research. 
 
Intercurrent illnesses or injuries should be regarded as adverse events.  Abnormal results of diagnostic 
procedures are considered to be adverse events if the abnormality: 
• 
results in study withdrawal 
• 
is associated with a serious adverse event 
• 
is associated with clinical signs or symptoms 
• 
leads to additional treatment or to further diagnostic tests 
• 
is considered by the investigator to be of clinical significance 
 
Serious Adverse Event (SAE) 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that:  
• 
results in death; 
• 
is life-threatening (places the subject at immediate risk of death from the event as it occurred); 
• 
results in inpatient hospitalization or prolongation of existing hospitalization; 
• 
results in a persistent or significant disability/incapacity; 
• 
results in a congenital anomaly/birth defect; or 
• 
based upon appropriate medical judgment, may jeopardize the subject’s health and may require medical 
or surgical intervention to prevent one of the other outcomes listed in this definition (examples of such 


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events include allergic bronchospasm requiring intensive treatment in the emergency room or at home, 
blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse). 
 
Unanticipated Problems Involving Risk to Subjects or Others (UPIRSO) 
Any incident, experience, or outcome that meets all of the following criteria:  
• 
Unexpected in nature, severity, or frequency (i.e. not described in study-related documents such as the 
IRB-approved protocol or consent form, the investigators brochure, etc.) 
• 
Related or possibly related to participation in the research (i.e. possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the procedures 
involved in the research) 
• 
Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
 
Adverse Event Reporting Period 
The study period during which adverse events must be reported is normally defined as the period from the 
initiation of any study procedures to the end of the study treatment follow-up.  For this study, the study treatment 
follow-up is defined as 7 days following the last administration of study treatment.  
 
Pre-existing Condition 
A preexisting condition is one that is present at the start of the study.  A pre-existing condition should be recorded 
as an adverse event if the frequency, intensity, or the character of the condition worsens during the study period. 
 
General Physical Examination Findings 
At screening, any clinically significant abnormality should be recorded as a preexisting condition.  At the end of 
the study, any new clinically significant findings/abnormalities that meet the definition of an adverse event must 
also be recorded and documented as an adverse event.  
 
Abnormal Laboratory Values 
A clinical laboratory abnormality should be documented as an adverse event if any one of the following conditions 
is met:  
• 
The laboratory abnormality is not otherwise refuted by a repeat test to confirm the abnormality 
• 
The abnormality suggests a disease and/or organ toxicity 
• 
The abnormality is of a degree that requires active management; e.g. change of dose, discontinuation of 
the drug, more frequent follow-up assessments, further diagnostic investigation, etc. 
 
Hospitalization, Prolonged Hospitalization or Surgery 
Any adverse event that results in hospitalization or prolonged hospitalization should be documented and reported 
as a SAE unless specifically instructed otherwise in this protocol.  Any condition responsible for surgery should 
be documented as an AE if the condition meets the criteria for and adverse event. Neither the condition, 
hospitalization, prolonged hospitalization, nor surgery are reported as an AE in the following circumstances: 
• 
Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures for a preexisting 
condition.  
• 
Surgery should not be reported as an outcome of an adverse event if the purpose of the surgery was 
elective or diagnostic and the outcome was uneventful. 
• 
Hospitalization or prolonged hospitalization required to allow efficacy measurement for the study. 
• 
Hospitalization or prolonged hospitalization for therapy of the target disease of the study, unless it is a 
worsening or increase in frequency of hospital admissions as judged by the clinical investigator. 


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8.2. Recording and Reporting of Adverse Events and Protocol Deviations 
At each contact with the subject, the investigator or study staff will seek information about adverse events by 
specific questioning and, if appropriate, by examination.  The principal investigator will review the safety and 
progress of this study on a continuing basis. Safety data will be reviewed at each study visit. Information on all 
adverse events will be recorded immediately in the source document, and also in the appropriate adverse event 
section of the case report form.  
 
• 
AEs will be tracked using the HSC IRB AE tracking form or data management tool (See Section 9.3) to 
be reviewed by Site Investigator weekly and IND Sponsor monthly. 
 
• 
All AEs occurring during the study period will be recorded. The clinical course of each event will be 
followed until resolution, stabilization, or until it has been determined that the study treatment or 
participation is not the cause.   
 
• 
All adverse events will be summarized annually and submitted to the IRB.   
 
• 
Deviations from the approved protocol (PDs) will be recorded in the site Protocol Deviation Log. When a 
deviation occurs site investigators or research staff will notify the site IRB and the IND sponsor as 
appropriate per local policy and procedure. 
 
• 
The IND Sponsor records every PD in a study-wide log and reviews within 48 hours of notification to 
determine if prompt reporting to IRB of record  is required.  
 
8.3. Recording and Reporting of Serious Adverse Events and Unanticipated Problems 
 
SAEs and UPIRSOs will be reported per governing IRB policy and procedure. 
• 
UPIRSOs that are a result of study participation are reported to the IRB and the Medical Safety Officer 
within 24 hours. The report will include a description of the event, when and how it was reported, as well 
as any official chart records or documentation to corroborate the event or the reporting of the event. All 
adverse events will be graded as mild, moderate, or severe.   
• 
SAEs will also be submitted to the IRB and the safety officer within 24 hours.  
• 
SAEs that are still ongoing at the end of the study period will be followed up to determine the final outcome.  
Any SAE that occurs after the study period and is considered to be possibly related to the study treatment 
or study participation will be recorded and reported per Institutional policy and according to FDA 
requirements. 
 
Any action resulting in a temporary or permanent suspension of this study (e.g. local site IRB actions) will be 
reported to the IND Sponsor. 
Investigator reporting: notifying the IND sponsor 
Any study-related UPIRSO, and any type of SAE, must be reported to IND Sponsor by telephone within 24 hours 
of the event.  To report such events, a Serious Adverse Event (SAE) form must be completed by the investigator 
and faxed to IND sponsor within 24 hours.  The investigator will keep a copy of this SAE form on file at the study 
site.   
 
Report SAE/UPIRSOs by email or facsimile to: 
 
Sara E. Espinoza, MD 
Associate Professor, Department of Medicine 


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University of Texas Health Science Center at San Antonio 
Barshop Institute for Longevity and Aging Studies 
7703 Floyd Curl Drive 
Mail Code 7886 
San Antonio, Texas 78229-3900 
(210) 617-5197 (phone) – (210) 562-6130 (fax) 
Email: espinozas2@uthscsa.edu 
 
Within the following 48 hours, the investigator must provide further information on the SAE or the UPIRSO in the 
form of a written narrative.  This should include a copy of the completed SAE form, and any other diagnostic 
information that will assist the understanding of the event.   
 
Reporting Process: Notifying the UTHSCSA IRB 
Adverse events not requiring immediate reporting may be tracked at each site on UTHSCSA Adverse Event 
Tracking Form (Track both UPIRSO and Events and Problems Not Requiring Prompt Reporting) and will be 
collected in REDCap. For SAE and UPIRSO, use UTHSCSA Prompt Reporting Form. 
Sponsor reporting: Notifying the FDA 
• 
Within 7 calendar days 
Any study event that is: 
– associated with the use of the study drug 
– unexpected,  
– fatal or life-threatening, and  
 
• 
Within 15 calendar days 
Any study event that is: 
– associated with the use of the study drug, 
– unexpected, and 
– serious, but not fatal or life-threatening 
-or- 
– previous adverse event that was not initially deemed reportable but is later found to fit the criteria for 
reporting (reporting within 15 calendar days from when event was deemed reportable). 
Any finding from tests in laboratory animals that:  
– suggest a significant risk for human subjects including reports of mutagenicity, teratogenicity, or 
carcinogenicity. 
 
Sponsor Reporting Process 
Serious adverse events may be submitted on FDA Form 3500A or in a narrative format. The contact information 
for submitting IND safety reports is noted on the next page. 
 
Food and Drug Administration 
Center for Drug Evaluation and Research 
Division of Metabolism and Endocrinology Products 
5901-B Ammendale Road 
Beltsville, MD 20705-1266 
Phone: (301) 796-2290 
Fax: (301) 796-9712  
8.4. Medical Monitoring 
The IND Sponsor will review the safety and progress of this study on a monthly basis or when needed if SAE 


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or SAE-UPIRSO occurs.  The Medical Safety Officer isDean L. Kellogg, Jr.,, M.D., Ph.D., Professor, Division 
of Geriatrics, Gerontology and Palliative Medicine in the Department of Medicine.    
 
Contact information: (see next page) 
Dean L. Kellogg, Jr., , M.D., Ph.D., Professor, Department of Medicine 
Division of Geriatrics, Gerontology and Palliative Medicine 
University of Texas Health Science Center at San Antonio 
7703 Floyd Curl Drive 
Mail Code 7875 
San Antonio, Texas 78229-3900 
(210) 617-5197 (phone) – (210) 562-6130 (fax) Email: kellogg@uthscsa.edu 
8.5. Unblinding Procedures 
See Section 8.3 – For SAE or SAE-UPIRSO, the site investigator must report within 24 hours of the event to IND 
Sponsor who confers with Medical Safety Officer (Section 8.4) to assess the need for initiation of stopping rules 
or unblinding procedures. Responsibilities of each individual are bulleted below. 
Medical Safety Officer 
• 
Assess SAE or SAE-UPIRSO to determine if unblinding is required and, if yes, notify pharmacist to 
request subject’s assignment 
• 
Compare event data to intervention/assignment to determine if SAE is related to study intervention 
• 
Assess study and subject safety to determine if stopping rules should be invoked 
• 
Create the Safety Officer record in a blinded report format and communicate to Sponsor and with overall 
impression and recommended plan of action 
• Responsible for determining the need to “unblind” the site investigator 
 
Research Pharmacist  
• 
Upon request, if necessary, unblind subject assignment and communicate to Medical Safety Monitor  
• 
Suspend dispensing of study drug until SAE reporting is complete 
 
Sponsor 
 
• Receive and review Medical Safety Officer report with Pharmacist and Study Statistician 
• 
Determine and implement stopping rules by communicating to site investigators, if required 
• 
Ensure that IRB, FDA, and funding sponsors are notified as appropriate to local or agency policy 
• 
Provide a copy of Medical Safety Officer report/record to appropriate personnel to file in eRegulatory 
Binder  
 
Clinical Study Coordinator  
 
• 
Ensure appropriate medical care and follow up is scheduled and implemented until SAE resolved 
8.6. Stopping Rules  
 
In the unlikely event that a study-related death or SAE occurs, the decision to stop the trial, either temporarily 
or permanently, will be the responsibility of the Medical Safety Officer in collaboration with the IND Sponsor. 
 
Clinical excursions that a subject may experience that may warrant stopping study participation or drug 
administration either temporarily or permanently include but are not limited to: 
 


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• 
Clinical criteria: 
– Fever with a temperature > 101°F or other clinical indication of active illness 
– Blood pressure >170/95 or <90/50 
– Allergic reaction to drug 
– Serious nosebleeds or other localized side effects of drug administration 
– Hyponatremia (serum sodium < 135 mmol/L) and/or low serum osmolality (serum osmolality < 275 
mOsm/kg).  
o Obtain serum sodium levels and osmolality at any time hyponatremia is suspected based on 
symptoms lethargy, muscle spasms, seizures, confusion/delirium, nausea and vomiting or 
physical examination  
o Any patient withdrawn from the study or has low sodium levels at the final visit will be evaluated 
until full normalization of the electrolyte abnormality occurs, and clinical and laboratory evaluations 
will be made available to medical safety monitor for review. 
– Other Serious Adverse Event adjudicated by medical safety monitor and invoking stopping rules 
 
9. Data Handling and Record Keeping 
9.1. Confidentiality 
Information learned about all subjects will be kept confidential.  All data and protected health information (PHI) 
in paper form will be kept confidential by assigned anonymous identifier and kept secured (password protected 
and/or double locked). Subjects will not be identified in any way in any publication.   
9.2. Source Documents 
Source data are contained in source documents found in paper subject files at the research site and in site 
electronic medical records.  If source data are handwritten, print all entries legibly in black ink.  Erasures and 
white-out material are prohibited. If any entry error has been made on paper, to correct such an error, draw a 
single straight line through the incorrect entry and enter the correct data above it.  All such changes must be 
initialed and dated.  For clarification of illegible or uncertain entries, print the clarification above the item, then 
initial and date it. 
9.3. Data Management 
 
Data System: REDCap 
All data will be input using a web front-end interface. All users are individually assigned authorization for access 
to specific components of the database application. Information that is input is checked for logical and range 
consistency and mandatory data fields must be entered in order to input a record. Reports are available as Excel 
exports to each site staff with access to reports. 
 
Case Report Forms 
CRFs will be developed in REDCap and may be printed in PDF for handwritten use. Radiology and lab reports 
may be printed or copied for use as source documents, while questionnaires and validated instruments may 
be copied from the Manual of Operations (MOP) for use in the paper research record. Data entry personnel 
will be appropriately trained before study is initiated. 
9.4. Records Retention 
The IND Sponsor is responsible for maintaining the Trial Master File by way of access to and storage in the 
eRegulatory Binder at Clinical Trials Express. 
 
The local site Principal Investigator is responsible for maintaining study essential documents for at least 3 years 
after study participation ends for the last subject at the last site, or according to the IND Sponsor’s institutional 


OXY-SAR-001 
 
 
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retention period, whichever is greater.  
 
These documents should be retained for a longer period if required by a funding agency, the FDA or other 
institutional retention policy.  In such an instance, it is the responsibility of the IND Sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained.  
 
10. Study Monitoring, Auditing, and Inspecting 
10.1. Study Monitoring Plan 
The Sponsor will ensure that the designated study monitor, compliance specialist or other quality assurance 
reviewer is given access to all the above noted study-related documents and study related facilities (e.g. 
pharmacy, diagnostic laboratory, etc.), and has adequate space to conduct the study monitoring visits. 
 
Monitoring elements will be reviewed at least once during the study period as described below: 
• 
Consent process 
• 
Accuracy of the collection and processing of laboratory specimens  
• 
Forms and source documents in the subjects’ research records will be current and maintained in a timely 
manner. 
• 
Physical and mental condition of the subject and any type of AE will be assessed and monitored prior to 
beginning the study by the investigator(s) and staff, and during the study period. 
 
Areas of focus for study monitoring by the designated study monitor: 
• 
Regulatory documentation and compliance with local policy will be monitored once during the study period 
at each site.  
• 
The safe handling and accountability of drugs, which includes the use of temperature logs and disposal 
of waste, will be maintained upon receipt of study drug, upon dispensing, and at the close out of the study 
period. 
• 
Compliance with the protocol and conduct of the study, including the consenting process, along with 
source data compared to collected data (SDV), will be monitored once at each site during the study period.  
– 30% of subject records and 100% of primary outcome data for each subject at each site will be 
monitored.  
– The first and the last subject enrolled will be monitored for consent practices and 100% of eligibility 
data collected. 
• 
Adverse event logs will be monitored and research records analyzed for AEs that were overlooked or 
otherwise not documented properly in the study files. 
• 
The safety assurance and condition of any electrical, radiological, magnetic, gaseous, and hazardous 
equipment, tools or apparatus that will be used by the investigators and subjects at each site will be 
properly maintained and certified by the site’s biomedical safety staff on at least an annual basis. The 
local site PI will attest to this assurance prior to enrolling the first subject. 
 
10.2. Auditing and Inspecting 
The site Investigator will permit study-related monitoring, audits, and inspections by the IRB, the funding 
sponsor, government regulatory bodies, and University compliance groups of all study related documents (e.g. 
source documents, regulatory documents, data collection instruments, study data etc.).  The site investigator 
will ensure the capability for inspections of applicable study-related facilities (e.g. pharmacy, diagnostic 
laboratory, etc.). 
 
Participation as a site investigator in this study implies acceptance of potential inspection by government 


OXY-SAR-001 
 
 
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regulatory authorities and applicable University compliance and quality assurance offices. 
11. Ethical Considerations 
This study is to be conducted according to US and international standards of Good Clinical Practice (FDA Title 
21 part 312) applicable government regulations and Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to the governing Institutional Review Board (IRB), in 
agreement with local legal prescriptions, for formal approval of the study conduct.  The decision of the IRB 
concerning the conduct of the study will be made in writing to the investigator(s) before the study is initiated. 
 
All subjects for this study will be provided a consent form describing this study and providing sufficient 
information for subjects to make an informed decision about their participation in this study.  See Attachments, 
Section 15, Attachment B., Sample Informed Consent Form.  This consent form will be submitted with the 
protocol for review and approval by the IRB for the study.  The formal consent of a subject, using the IRB-
approved consent form, must be obtained before that subject undergoes any study procedure.  The consent 
form must be signed by the subject or legally authorized representative, and the IRB-approved research 
professional obtaining the consent.  
12. Study Finances 
12.1. Funding Source 
In San Antonio, this study is financed through a grant from the US National Institutes of Health/National Center 
for Advancing Translational Sciences (NIH/NCATS). Each site is responsible for its own funding of the study, 
including study drug supply. 
12.2. Conflict of Interest 
None reported (see Forms FDA 3455 on file in CTX eRegulatory Binder) 
12.3. Subject Stipends or Payments 
This study will reimburse subjects for time and transportation.  A schedule of payments is shown below. The 
total potential reimbursement to a subject is $630 for the study for all visits including both optional MRIs ($480 
without MRI). Payments may be prorated to include the last visit completed if study participation is terminated 
early. Manual payments for additional or partial visits, if necessary, will be handled on an ad-hoc basis with 
prior approval from the funding sponsor.See Payment Schedule in the table below. 
 
Visit 1  
$  75 
Visit 2 (optional) 
$  75 
Visit 3  
$  150 
Visit 4  
$  15 
Visit 5 
$  30 
Visit 6 
$  60 
Visit 7 (optional) 
$  75 
Visit 8  
$  150 
Manual Payment for an 
Interim Visit 
Up to $ 30 
 
 
 


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13. References 
 
 
1. 
Lawson E, Marengi D, DeSanti R, Holmes T, Schoenfeld D, Tolley C. Oxytocin reduces caloric intake in 
men. Obesity. 2015; 23:950-956. 
 
2. 
Zhang H, Wu C, Chen Q, et al. Treatment of obesity and diabetes using oxytocin or analogs in patients 
and mouse models. PLoS ONE. 2013; 8(e61477):1-11. 
 
3. 
Borg J, Simren M, Ohlsson B. Oxytocin reduces satiety scores without affecting the volume of nutrient 
intake or gastric emptying rate in healthy subjects. Neurogastroenterol Motil. 2011; 23:56-e5. 
 
4. 
Elabd C, Cousin W, Upadhyayula P, et al. Oxytocin is an age-specific circulating hormone that is 
necessary for muscle maintenance and regeneration. Nature Communications. 2014; 5:4082. 
 
5. 
Meyer-Lindenberg A, Domes G, Kirsch P, Heinrichs M. Oxytocin and vospressin in the human brain: Social 
neuropeptides for translational medicine. Nature Reviews Neuroscience. 2011; 12:524-538. 
 
6. 
Leng G, Ludwig M. Intranasal oxytocin: Myths and delusions. Biological Psychiatry. 2016; 79:243-250. 
 
7. 
Iwasaki Y, Maejimi Y, Suyama S, et al. Periperal oxytocin activates vagal afferent neurons to suppress 
feeding in normal and leptin-resistant mice: A route for ameliorating hyperphagia and obesity. Am J Physiol 
Regul Integr Comp Physiol. 2015; 308:R360-R369. 
 
8. 
Finger E, MacKinley J, Blair M, et al. Oxytocin for frontotemporal dementia: A randomized dose-finding 
study of safety and tolerability. Neurology. 2015; 84:181. 
 
9. 
Kane R, Shamliyan T, Talley K, Pacala J. The association between geriatric syndromes and survival. J Am 
Geriatr Soc. 2012; 60:896-904. 
 
10. Kallman D, Plato C, Tobin J. The role of muscle loss in the age-related decline of grip strenth: Cross-
sectional and longitudinal perspectives. Journal of Gerontology: Medical Sciences. 1990; 45:M82-88. 
 
11. Blau H, Cosgrove B, Ho A. The central role of muscle stem cells in regenerative failure with aging. Nature 
Medicine. 2015; 8:854-862. 
 
12. Fielding R, Vellas B, Evans W, et al. Sarcopenia; an undiagnosed condition in older adults. current 
consensus definition: Prevalence, etiology, and consequences. international working group on sarcopenia. 
J Am Med Dir Assoc. 2011; 12:249-256. 
 
13. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: 
Comparison with the euglycemic insulin clamp. Diabetes Care. 1999; 22:1462-1470. 
 
14. Womble L, Wadden T, Chandler J, Martin A. Agreement between weekly vs. daily assessment of appetite. 
Appetite. 2003; 40:131-135. 
 
15. Shim J, Oh K, Kim H. Dietary assessment methods in epidemiologic studies. Epidemiology and Health. 
2014; 36:e2014009. 
 
16. Ghosh S, Lertwattanarak R, Garduno J, et al. Elevated muscle TLR4 expression and metabolic 
endotoxemia in human aging. Journals of Gerontology: Medical Sciences. 2015; 70:232-246. 


OXY-SAR-001 
 
 
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17. Sriwijitkamol A, Coletta DK, Wajcberg E, et al. Effect of acute exercise on AMPK signaling in skeletal 
muscle of subjects with type 2 diabetes. Diabetes. 2007; 56:836-848. 
 
18. Li M, Verdijk LB, Sakamoto K, Ely B, van Loon LJ, Musi N. Reduced AMPK-ACC and mTOR signaling in 
muscle from older men, and effect of resistance exercise. Mechanisms of Ageing & Development. 2012; 
133:655-664. 
 
19. Snijders T, Verdijk L, Smeets J, et al. The skeletal muscle satellite cell response to a single bout of 
resistance-type exercise is delayed with aging in men. Age (Dordr). 2014; 36:9699. 
 
20. Billin A, Bantscheff M, Drewes G, et al. Discovery of novel small molecules that activate satellite cell 
proliferation and enhance repair of damaged muscle. ACS Chem Biol. 2016; 11:518-529. 
 
21. Hussey SE, Liang H, Costford SR, et al. TAK-242, a small molecule inhibitor of toll-like receptor-4 
signaling, unveils similarities and differences in lipopolysaccharide- and lipid-induced inflammation and 
insulin resistance in muscle cells. Bioscience Reports. 2013; 33:37-47. 
 
22. MacDonald E, Dadds M, Brennan J, Williams K, Levy F, Cauchi A. A review of safety, side-effects and 
subjective reactions to intranasal oxytocin in human research. Psychoneuroendocrinology. 2011; 36:1114-
1126. 
 
23. Guralnik J, Simonsick E, Ferrucci L, Glynn R, Berkman L, Blazer D, Scherr P, Wallace R. A short physical 
performance battery assessing lower extremity function. Journal of Gerontology; Mar 1994; 49: M85-M94. 
 
24. Podsiadlo D and Richardson S. The timed “up and go”: a test of basic functional mobility for frail elderly 
persons. J Amer Geriatr Soc; 1991; 39(2): 142-148. 
 
25. Klopfenstein, B J et al. Comparison of 3 T MRI and CT for the Measurement of Visceral and Subcutaneous 
Adipose Tissue in Humans. Br J Radiol; 2012: 85(1018): e826–e830. 
 
 
 
14. Attachments 
A. Consent Form Template – page 23 
B. Event Schedule – page 24 
C. Victoria Apotheke Zurich: Syntocinon, Drug information – page 25 
D. Placeholder for Questionnaires, Instruments & Forms – page 26 
E. Summary of Protocol Changes – page 27, 28 
 
 
 
 
 
 
 


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ATTACHMENT A.  PLACEHOLDER FOR SAMPLE CONSENT FORM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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ATTACHMENT B.  EVENT SCHEDULE 
  
Visit 1 
Visit 2 
Visit 3 
Visit 4* 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
  
Screen 
Day 0 
MRI 
+7 days 
V2 
+7-14 
days 
1 week 
on Rx 
4 weeks 
on Rx 
6-7.5 
weeks on 
Rx 
7-7.5  
weeks 
on Rx 
7.5-8 
weeks on 
treatment 
Medical history and physical 
examination, ECG 
X 
  
  
  
  
  
  
  
Vital signs, Weight, BMI,  
X 
  
 X 
X  
X  
X 
 
 X 
Waist circumference 
X 
  
 
X  
X  
X 
 
 X 
Mini-mental status exam (Mini-
Cog) 
X 
  
  
  
  
  
  
  
Montreal 
Cognitive 
Assessment (MoCA) 
X 
 
 
 
X 
 
 
X 
Geriatric 
depression 
scale 
(GDS) 
X 
 
 
 
 
 
 
 
Centers 
for 
Epidemiologic 
Studies Depression Scale 
X 
 
 
 
X 
 
 
X 
Gait speed, 15-foot course 
X 
  
  
  
  
 X 
  
  
**Hematology (CBC, HgbA1c) 
and 
Coagulation 
testing 
(PT/INR, PTT) 
X 
  
  
  
  
 X 
 
  
**Chemistry with liver function 
and serum osmolality 
X 
  
 
X  
X 
X 
 
  
**Lipid Panel 
X 
 
 
 
 
X 
 
 
**Urinalysis 
X 
  
  
  
  
  
  
  
**Urine osmolality 
X 
  
  
 X 
 X 
X 
 
  
Electrocardiogram  
X 
 
 
 
 
 
 
 
OGTT, 2 hour 
X 
 
 
 
 
X 
 
 
Body composition (DEXA) 
  
 
X 
  
  
  
 
X 
Bioimpedance (UTMB only) 
  
 
X 
  
  
  
 
X 
Calorimetry 
  
 
X 
  
  
  
 
X 
Randomization 
 
 
X 
 
 
 
 
 
Body composition (MRI) 
 
X 
X 
 
 
 
X 
 
Functional 
tests: 
mSPPB, 
TUG, grip strength 
 X 
 
  
  
  
 X 
 
  
24-hour food recall, 3-day food 
diary, appetite 
 X 
 
  
X  
X  
X 
 
  
Muscle biopsy: satellite cell, 
fiber 
type, 
fat 
infiltration, 
inflammation, gene expression 
  
 
X 
  
  
  
 
X 
Systemic inflammation 
  
 
X 
  
  
  
 
X 
Drug tolerability/ compliance, 
adverse event monitoring 
  
  
AE review 
only  
X  
X 
X 
 
X 
* After Visit 4, participants may receive periodic phone calls by study staff between study visits to assess any 
symptoms and encourage adherence to study drug. 
** Any marginally abnormal lab findings may be repeated if clinically indicated to ensure initial or continued 
eligibility. 
 
 


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ATTACHMENT C.  PLACEHOLDER FOR VICTORIA APOTHEKE ZURICH  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ATTACHMENT D.  PLACEHOLDER FOR QUESTIONNAIRES, INSTRUMENTS, & FORMS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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ATTACHMENT E.  SUMMARY OF PROTOCOL CHANGES 
 
Date of Change  
Version # 
Section Modified  
Before Change  
After Change  
11-21-2016  
1.1  
Title Page  
 
All pages 
 
 
3.4 Potential Risks 
 
 
 
4.2 Exclusion Criteria 
 
 
 
 
 
 
 
 
 
 
6.1 Consent and 
Screening Visit 1, page 9 
 
 
6.3 Visit 3, page 10 
 
 
 
 
 
 
 
 
 
 
6.4 Visit 4, page 11 
 
 
 
6.5 Visit 5,+4 weeks from 
V4 
 
 
 
 
 
Section 6, Study Visits 
 
 
8.6, Stopping Rules 
IND Number: Pending  
 
 
 
 
Rare: Nausea, 
dermatitis, uterine 
contractions 
 
Renal disease 
(Creatinine >1.4) 
 
 
 
 
 
 
 
 
 
Screening labs did not 
include urinalysis, urine 
or serum osmolality 
 
No safety labs 
mentioned at this visit 
 
 
 
 
 
 
 
 
 
Safety labs: CBC and 
CMP 
 
 
Labs: CBC, CMP, 
cholesterol panel, 
HgbA1c, coagulation 
tests, and systemic 
inflammatory markers 
 
No embedded Visit and 
Procedures Schedule 
 
No mention of 
hyponatremia or fluid 
imbalance 
IND Number: 132460-0001  
 
General spacing, formatting, pagination 
and header/footer changes 
 
(FDA requested change) – Rare: added 
hyponatremia and or fluid imbalance 
 
 
(FDA requested change) Renal disease: 
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;  
Individuals with underlying seizure 
disorder or underlying neurologic disorder 
that increases seizure risk 
 
(FDA requested change) Added 
urinalysis, urine and serum osmolality to 
screening labs 
 
(FDA requested change) Visit 3a, 3b, 3c 
created and safety review/labs added at 
3c. 
Visit 3a: Blood draw for systemic 
inflammatory markers 
Visit 3b: Optional MRI 
Visit 3c. Safety review/labs: Chemistry, 
including serum sodium and serum 
osmolality and drug tolerability 
assessment 
 
(FDA requested change) Added urinalysis 
and serum osmolality at 4 weeks of drug 
therapy; removed CBC  
 
Assigned safety labs to 6.5.1 Visit 5a – 
Laboratory: CBC, CMP, urinalysis, serum 
osmolality, lipid panel, HgbA1c, 
coagulation tests (PT, INR, PTT) 
 
 
Added Table 3, page 13. 
 
 
(FDA requested change) Added to clinical 
criteria the clinical values for stopping due 
to hyponatremia or changes in fluid 
balance 


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12-15-16 
1.2 
Throughout document 
 
Title Page 
 
 
 
 
 
 
 
Table of Contents 
 
 
3.2 General Study Design 
 
3.4 Potential Risks to 
Subject Safety 
 
 
 
 
 
 
4.3 Subject Recruitment 
and Screening 
 
 
 
 
 
6.1 Study Procedures 
 
 
 
 
 
6.2 Baseline 
 
 
 
 
 
6.3. 
 
 
 
6.5  
 
 
 
 
 
 
10.1, Study Monitoring 
Plan 
 
 
12, Study Finances 
 
 
 
14, Attachments 
 
Title of Study: 
Physiological… 
 
Clinical Sites and 
Coordinating Center 
 
 
No Attachment E. 
 
Page numbering not 
hyperlinked 
 
Phase I/II 
 
Blood Withdrawal, page 
4 includes details about 
blood being drawn.  
 
IV Lines, page 4: 
…antecubital vein and a 
hand vein… 
 
…performed in 
CRCs…Subjects will be 
screened for eligibility 
using an initial phone 
screen. 
 
 
6.1 Visit 1, Consent and 
Screening Day 0 
 
 
 
 
6.2 Baseline 
 
 
 
 
 
6.3 Visit 3a. 
 
 
 
6.5 Visit 5 
 
Table 3. Study Visits 
and Procedures missing 
a few items 
 
 
Areas of focus for study 
monitoring… 
 
12.3, Subject Stipends 
or Payments, …total 
potential reimbursement 
of $770 
 
Attachments A, B, C, D 
 
Formatting and space revisions 
 
Changed title of study to “Physiologic”  
 
Changed UTHSCSA to new brand name 
UTHealth San Antonio  
Added Clinical Trials Express -
Coordinating Center 
Added Attachment E. Summary of 
Protocol Changes 
Added hyperlinks to page numbers 
 
 
Changed to “Phase II pilot” 
 
Removed detailed lab tests and inserted 
more general statement that blood will be 
drawn for safety and for research 
purposes at screening and or study visits. 
 
Deleted “and” and inserted “or” 
 
 
Changed to read: At some sites, subjects 
will call-in to an advertised number and 
will be pre-screened…callers provide 
permission for research team to follow up 
with phone screening using an IRB-
approved form… 
 
6.1 Visit 1 (Consent and Screening for 
Eligibility – Day 0) 
 
Added estimated length of this visit is 5 
hours at the end of paragraph 1. 
 
Changed to read Baseline Testing 
 
Moved Grip Strength bullet to fall within 
Functional Testing along with other 
assessments. 
 
Changed subheading to 6.3 Visit 3a-c: 
Physiological measures, Randomization 
and optional MRI 
 
Changed subheading to 6.5 Visit 5a-c: 
 
Table 3. Added history and physical, 
added MMSE, separated blood and urine 
labs into separate rows and visits 
accordingly 
 
Added to 2nd bullet on drug accountability 
to insert “upon dispensing”… 
 
…changed total to $660 with both MRIs, 
and $510 without MRIs. Subject payment 
table changed per visit accordingly.  
 
 
Changed title of Attachment D  


OXY-SAR-001 
 
 
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12-15-16 
1.2.1 
 
 
Internal changes only: Incorporated into 
and saved as v1.2 above 
12-19-16 
1.2.2 
6.1-6.5 Study Procedures 
 
Changed Visit 1 MMSE to Mini-Cog, 
extended Gait measure from 10 feet to 
15-foot course.  
 
Added MoCA to Visit 2  
 
Added food and appetite measures at 
Visit 3c and Visit 4 and deleted them at 
Visit 5a.  
 
Modified Visit table accordingly. 
 
 
 
 
 
12-20-16 
 
 
 
 
 
 
 
1.2.3 
ATTACHMENT E. 
Summary of Protocol 
Changes Table 
 
8.4 Medical Monitor 
 
 
 
ATTACHMENT B. 
Placeholder for Event 
Schedule 
 
 
 
 
8.4, Page 16 
 
 
 
ATTACHMENT 
B., Event Schedule 
Updated all changes to date by version 
in the Summary table. 
 
 
Added “Contact Information: (see next 
page)” before listing his address, etc. 
on page 17 
 
Inserted Event Schedule from Page 
12, Table 3, Study Visits and 
Procedures; corrected event schedule 
in 2 places to be consistent with ICF 
 
03-17-17 
1.2.4 
Table of Contents 
Update Visit Numbers 
Renumbered Visit 3a-c, 4, 5a-c to 
visits 3-9 
 
 
3.1 
Definition of Sarcopenic 
Obesity  
Updated definition of Sarcopenic 
Obesity to reflect modified consensus. 
Muscle mass will be measured as an 
outcome.  
 
 
6.3-6.5.3 
Update Visit Numbers 
Renumbered Visit 3a-c, 4, 5a-c to 
visits 3-9 
 
 
Table 3 
Study Visits and 
Procedures 
Renumbered Visit 3a-c, 4, 5a-c to 
visits 3-9 
 
 
Table 12.3 
Subject Stipend 
Renumbered Visit 3a-c, 4, 5a-c to 
visits 3-9 
 
 
ATTACHMENT B 
ATTACHMENT B 
Renumbered Visit 3a-c, 4, 5a-c to 
visits 3-9 
 
 
 
 
 
05-16-17 
2.0 
4.2 Exclusion Criteria 
4.3 
6.1c 
GDS > 5 
GDS > 7 
 
 
 
 
 
 
 
4.3 
Screening tests 
Remove ECG 
 
 
 
 
 
 
 
6.1 
Visits 1 and 2 
Combined to Visit 1, remove ECG, 
deleted unnecessary language 
 
 
 
 
 
 
 
6.1-6.8 
Update Visit Numbers 
Renumbered Visit 1-8 
 
 
 
 
 
 
 
Table 3 
Study Visits and  
Renumbered Visit 1-8, removed ECG,  
 
 
 
 
 
 
 
Table 12.3 
Subject Stipend 
Renumbered Visit 1-8 
 
 
 
 
 
 
 
ATTACHMENT B 
ATTACHMENT B 
Same as Table 3,  
 
 
 
 
 
 
 
Summary of Protocol 
Changes Table. 
 
Updated to V2.0 all changes to 
protocol shown above 
 
 
 
 
 
 
 
 
 
 


OXY-SAR-001 
 
 
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06-20-17 
2.1 
6.1 
Visit 1 
Added ECG back in 
 
 
 
 
 
 
 
6.2 and 6.3 
Visits 2 and 3 
Swapped visits 2 and 3 to have 
optional MRI occur before 
randomization. Provided PI discretion 
to forego optional MRI if necessary 
 
 
 
 
 
 
 
6.3 
Visit 3 
Baseline visit added to establish IV 
access for biopsy and UT Houston no 
calorimetry due to no equipment.  
 
 
 
 
 
 
 
6.7 and 6.8 
Visits 7 and 8 
Swapped visits 7 and 8 to have 
optional MRI occur before completion 
of study drug and final visit 
 
 
 
 
 
 
 
Visit Table 
Visit Table 
Swapped visit procedures to be 
consistent with narrative protocol 
 
 
 
 
 
 
 
Summary of Protocol 
Changes Table 
 
Updated to V2.1 all changes to 
protocol shown for 06-20-17 version 
 
 
 
 
 
10-03-17 
2.2 
Title Page, headers and 
footers 
Version number and 
IND series # 
Updating version numbering in header 
and footer to 2.2; IND# 0003 = v2.0 
protocol, 0004 = v2.1 protocol, 0005 = 
v2.2 this version to be consistent with 
recent IND reporting to FDA 
 
 
 
 
 
 
 
Study Summary page 1 
Inclusion/Exclusion 
Removed ADA criteria from diabetes 
exclusions, using A1c only; changed 
Serum creatinine measure to GFR for 
renal exclusion, changed urinalysis 
criteria for WBC and RBC; Significant 
heart disease (history of MI within 
the last year or New York Heart 
Classification grade III-IV) 
 
 
 
Page 2 and 4 
 
Spacing or format changes 
 
 
 
 
 
 
 
6.1 
Visit 1 
Inserted screening window of 30 days 
 
 
 
 
 
 
 
6.2 and 6.7 
Visits 2 and 7 
Inserted abdomen to MRI as well as 
dominant lower extremity 
 
 
 
 
 
 
 
6.3 and 6.8, and Visit table 
page 15 
Visits 3 and 8 
Changed bioimpedance to be offered 
only at UTMB Galveston 
 
 
 
 
 
 
 
Reference List 
Citation 25 
Corrected the reference to MRI of 
abdomen and lower extremity, adding 
citation number 25 
 
 
 
 
 
10-08-17 
2.2.1 
Title page and Summary of 
Changes table 
Administrative changes 
Added 03-24-17 as original approval; 
removed “(placeholder)’ from CTX 
address; updated versioning in 
headers and footers 
 
 
 
 
 


OXY-SAR-001 
 
 
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2.2.2 
Summary of Visits Table 
Repeat labs language 
Added spaces to create table on single 
page of its own. 
 
Added language to allow repeating 
marginally abnormal labs if clinically 
indicated to ensure initial or continued 
eligibility 
 
Changed periodic phone calls to occur 
after Visit 4 
 
Removed Optional from MRI and 
Baseline from V3 
 
 
 
 
 
 
 
Title page and footers 
Versioning 
Updated versioning throughout 
document to 2.2.2. 
 
 
 
 
 
11-17-17 
2.3 
Title page and footers 
Versioning 
Updated versioning throughout 
document to 2.3; IND series -0006 
added to title page 
 
 
 
 
 
 
 
Visit Section 6 and 
Summary Visit Table 
Procedures 
Added vital signs to Visits 1,3,4,5,6 
and 8 to narrative section 6 
 
 
 
 
 
 
 
Visit Section 6.4, 6.5, 6.6 
Labs 
Remove lipid panel from Visits 4 and 5 
narrative to be consistent with 
Summary Visit Table.  
 
Add urine osmolality to Visit 4 narrative 
to be consistent with other visits 
assessing osmolality and Summary 
Visit Table 
 
Change Visit 4, 5 and 6 referencing 
Visit 2 related to Food Recall to Visit 1. 
 
 
 
 
 
 
 
Visit Section 6.8 
Procedures 
Add Vital signs, weight, BMI, MOCA 
and CES-D to narrative to be 
consistent with Summary Visit Table 
 
 
 
 
 
 
 
 
 
Add drug compliance/tolerability, and 
AE review to Visit 8 narrative to be 
consistent with Summary Visit Table 
 
Add waist circumference to Visit 8 
narrative and to the Summary Table of 
Visits for consistency 
 
 
 
 
 
 
 
Section 12 
12.1 
Rephrasing each site responsible for 
its own funding, “including study drug 
supply.” 
 
 
 
 
 
 
 
General 
 
Revised pagination issues throughout 
the document 
 
 
 
 
 
04-03-18 
2.4 
Visits 1,3,4,5,6,8 narrative 
Fasting state 
Revised all visits to be consistent 
whenever there are labs drawn that 
subject presents to CRC in fasting 
state 
 
 
Visit Schedule 
(fasting) 
Change table to reflect fasting at Visits 
1,3,4,5,6,8 
 
 
Eligibility criteria 
30-40 kg/m2 
Change BMI range to 30.0-43.0 
 
 
 
 
 


OXY-SAR-001 
 
 
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08-03-18 
2.5 
Section 8.3-8.4 
Medical Monitoring 
Change Medical Safety Monitor to 
replace A. Fisher with Dean Kellogg, 
MD, PhD 
 
Add oversight by Pepper Center 
DSMB to review study progress and 
overall safety