Understanding Cognition, Oxytocin & Pain in Elders (UCOPE)

Mechanisms Underlying Oxytocin's Analgesia in Older Adults

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.

Study Overview

• Status: Recruiting
• Conditions: Osteoarthritis; Knee Osteoarthritis
• Intervention / Treatment: Drug: Oxytocin (OT); Drug: Placebo (P)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 370
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Yenisel Cruz-Almeida, PhD, MSPH; Phone Number: 352-294-5845; Email: cryeni@ufl.edu
• Study Contact Backup: Name: Natalie Ebner, PhD; Email: natalie.ebner@ufl.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • UF Health of University of Florida
    • Gainesville, Florida, United States, 32603
      • Recruiting
      • Department of Community Dentistry and Behavioral Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 43 years to 98 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oxytocin Crossover Placebo Group; 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); 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.; Drug: Placebo (P); 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.
Active Comparator: Placebo Crossover Oxytocin Group; 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); 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.; Drug: Placebo (P); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Yenisel Cruz-Almeida, PhD, MSPH, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2019
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): August 30, 2024

Study Registration Dates

• First Submitted: March 12, 2019
• First Submitted That Met QC Criteria: March 13, 2019
• First Posted (Actual): March 18, 2019

Study Record Updates

• Last Update Posted (Estimated): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: IRB201801467-N; R01AG059809 (U.S. NIH Grant/Contract); OCR18586 (Other Identifier: UF OnCore)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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