Understanding Cognition, Oxytocin & Pain in Elders

Study Overview
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Brief Summary
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Osteoarthritis (OA) represents a significant cause of disability worldwide and the knee is the most commonly affected joint. Oxytocin (OT) is a mediator of endogenous analgesia in animal and human studies. This proposal will test the efficacy and safety of self-administered intranasal OT over 4-weeks in older individuals relative to placebo (P) evaluating its effects on pain and function in aging and testing potential underlying neurobiological mechanisms.

Detailed Description
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Osteoarthritis (OA) represents a significant cause of disability worldwide in individuals aged 65 and older, a rapidly growing segment of our population. The knee is the most commonly affected joint with pain being the primary symptom, negatively impacting physical, cognitive, and emotional functioning. Symptomatic knee OA has been traditionally attributed to peripheral mechanisms, but measures of joint damage only modestly account for the presence or severity of OA-related pain. The neuropeptide oxytocin (OT) has been recognized as a mediator of endogenous analgesia in animal and human studies. However, little is known about the neurobiological mechanisms underlying OT's pain-relieving properties. This study will test the efficacy and safety of self-administered intranasal OT over 4-weeks in older individuals with knee osteoarthritis. Relative to placebo (P), daily administration of intranasal OT diminished self-reported pain, physical and emotional functioning and changes in brain metabolite concentrations. With strong support from the University of Florida and the McKnight Brain Institute, this interdisciplinary project, using a comprehensive multi-methods approach, will be the first to determine the potential benefit of OT as a novel analgesic therapy for knee OA pain in aging.

Official Title
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Mechanisms Underlying Oxytocin's Analgesia in Older Adults

Conditions
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Knee Osteoarthritis, Osteoarthritis

Intervention / Treatment
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* Drug: Oxytocin (OT)
* Drug: Placebo (P)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: knee osteoarthritis/or back pain of at least six months duration, experience pain on more days than not, with moderate pain at baseline (i.e., > 3/6 in the VDS), and who have elevated levels of plasma IL-6 (>2.5 pg/ml) will be considered for participation. Exclusion Criteria: Hypersensitivity to OT or vasopressin, history of hyponatremia, syndrome of inappropriate antidiuretic hormone secretion, or psychogenic polydipsia, on vasoconstrictors such as desmopressin, pseudoephedrine, or antidiuretic medication, low sodium and high osmolality levels, excessive smoking, excessive drinking, muscle pain as a result of systemic disease, significant nasal pathology, previous or concurrent use of narcotics delivered intranasally (e.g., cocaine), gastroparesis. individuals with heart problems (e.g., cardiomyopathy, history of myocardial infarction, arrhythmias, prolonged QT interval) Participants will also be excluded if they have concurrent medical or arthritic conditions that could confound symptomatic knee OA-related outcomes or coexisting disease that could preclude successful completion of the protocol including: systemic rheumatic condition (e.g. rheumatoid arthritis, systemic lupus erythematosus, fibromyalgia); a history of clinically significant surgery to the index knee; uncontrolled hypertension (>150/95); poorly controlled diabetes (HbA1c>7%); neurological disease (e.g., Parkinson's, Multiple Sclerosis); cardiovascular or peripheral arterial disease; serious psychiatric disorder requiring hospitalization within the past twelve months or characterized by active suicidal ideation; diminished cognitive function that would interfere with completion of study procedures (i.e., MoCA score < 25)]; and large pieces of metal in the body or metal in the face or neck, claustrophobia, major medical surgery in the past two months, history of brain surgery or any serious brain condition like aneurysm, stroke, or seizures]. pregnant individuals will be excluded

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This trial will be a double-blinded, randomized crossover group design that will randomize older adults with symptomatic knee OA pain to four weeks of intranasal self-administration of either oxytocin (OT) or placebo (P) (48 IUs daily) followed by a four-week washout period and a second four weeks of intervention (either OT or P).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oxytocin Crossover Placebo Group<br>During Phase 1 of the intervention, participants will self-administer via intranasal spray 24 IUs of oxytocin (OT) twice a day at home, at 8-9AM and again at 5-6PM. After a four-week washout period, Phase 2 will consist of a second four weeks of intervention, this time intranasal spray 24 IUs of placebo (P) twice a day will be self-administered. | Drug: Oxytocin (OT)<br>* During the 4 week intervention, participants will self-administer twice daily 24 IUs intranasal oxytocin (OT) and will be contacted once a week for assessment of adverse effects and for download of the smartwatch data. During the last week of the intervention period, three assessment sessions will follow that will be identical to the baseline sessions.<br>Drug: Placebo (P)<br>* During the 4 week intervention, participants will self-administer twice daily 24 IUs intranasal placebo (P) and will be contacted once a week for assessment of adverse effects and for download of the smartwatch data. During the last week of the intervention period, three assessment sessions will follow that will be identical to the baseline sessions.<br>|
| Active Comparator: Placebo Crossover Oxytocin Group<br>During Phase 1 of the intervention, participants will self-administer via intranasal spray 24 IUs of placebo (P) twice a day at home, at 8-9AM and again at 5-6PM. After a four-week washout period, Phase 2 will consist of a second four weeks of intervention, this time intranasal spray 24 IUs of oxytocin (OT) twice a day will be self-administered. | Drug: Oxytocin (OT)<br>* During the 4 week intervention, participants will self-administer twice daily 24 IUs intranasal oxytocin (OT) and will be contacted once a week for assessment of adverse effects and for download of the smartwatch data. During the last week of the intervention period, three assessment sessions will follow that will be identical to the baseline sessions.<br>Drug: Placebo (P)<br>* During the 4 week intervention, participants will self-administer twice daily 24 IUs intranasal placebo (P) and will be contacted once a week for assessment of adverse effects and for download of the smartwatch data. During the last week of the intervention period, three assessment sessions will follow that will be identical to the baseline sessions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis) Index | Self-reported pain and function. Summary scores of the WOMAC range from 0 (No pain or disability) to 96 (Extreme pain or disability). | Baseline; Week 1; Week 2; Week 3; Week 4; Week 9; Week 10; Week 11; Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Frontal Cortex Brain Metabolites | Track levels of the frontal cortex brain chemicals (tCr, MI, Cho) through use of magnetic resonance spectroscopy (MRS). | Baseline; Week 1; Week 2; Week 3; Week 4; Week 9; Week 10; Week 11; Week 12 |