Knee Osteoarthritis, Osteoarthritis
Conditions
Brief summary
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
Osteoarthritis 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 osteoarthritis has been traditionally attributed to peripheral mechanisms, but measures of joint damage only modestly account for the presence or severity of osteoarthritis-related pain. The neuropeptide oxytocin has been recognized as a mediator of endogenous analgesia in animal and human studies. However, little is known about the neurobiological mechanisms underlying oxytocin's pain-relieving properties. This study will test the efficacy and safety of self-administered intranasal oxytocin over 4-weeks in older individuals with knee osteoarthritis. Relative to placebo, daily administration of intranasal oxytocin 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 oxytocin as a novel analgesic therapy for knee osteoarthritis pain in aging.
Interventions
DRUGOxytocin (OT)
During the 4 week intervention, participants will self-administer twice daily 24 International Units 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.
DRUGPlacebo (P)
During the 4 week intervention, participants will self-administer twice daily 24 International Units 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.
Sponsors
University of Florida
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This trial will be a double-blinded, randomized crossover group design that will randomize older adults with symptomatic knee Osteoarthritis 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).
Eligibility
Sex/Gender
ALL
Age
45 Years to 100 Years
Healthy volunteers
No
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 Visual Descriptor Scale), and who have elevated levels of plasma Imterleukin-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 osteoarthritis-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., Montreal Cognitive Assessment 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in WOMAC Pain (0-20 Scale) | Baseline -> Week 4 | The WOMAC Pain subscale measures self-reported knee pain severity during daily activities. The subscale consists of 5 items assessing pain during walking, stair climbing, nocturnal pain, pain at rest, and weight-bearing activities. Each item is scored 0-4 (0=none, 4=extreme), yielding a total Pain subscale score of 0-20. Higher scores indicate greater pain severity. Change scores were calculated as post-treatment minus baseline; negative values indicate improvement (reduced pain). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORYenisel Cruz-Almeida, PhD, MSPH
University of Florida
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 67.1 years STANDARD_DEVIATION 9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 71 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 0 / 68 |
| other Total, other adverse events | 43 / 66 | 51 / 68 |
| serious Total, serious adverse events | 0 / 66 | 3 / 68 |
Outcome results
None listed