Maximizing Analgesia to Reduce Pain in Knee Osteoarthritis

Study Overview
=================
Brief Summary
-----------------
This research is being done to evaluate whether combining medications that are FDA approved, but have not yet been approved for combination treatment, can be effective in reducing pain.

Detailed Description
-----------------
This study will evaluate whether a combination of pharmacotherapies can effectively alleviate pain. Subjects will complete two screening sessions before completing four study sessions that will occur once weekly. Participants will receive double blind doses of study medications the morning of each experimental session day and will undergo standardized pain testing, physical functioning assessment, blood draws, ratings of drug effects and cognitive testing.

Official Title
-----------------
Maximizing Analgesia to Reduce Pain Sensitivity in Chronic Knee Osteoarthritis Pain Patients

Conditions
-----------------
Knee Osteoarthritis

Intervention / Treatment
-----------------
* Drug: Blinded study medication


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of knee osteoarthritis Urine sample tests negative for common illicit substances of abuse (e.g., cannabis) Medically cleared to take study medications Are not pregnant or breast feeding Willing to comply with the study protocol. Exclusion Criteria: Pain other than Knee Osteoarthritis Taking opioids for pain Prescribed and taking gabapentinoid, Tricyclic Antidepressants (TCA), venlafaxine, duloxetine, stimulants or benzodiazepines Presence of any clinically significant medical/psychiatric illness judged by the investigators to put subject at elevated risk for experiencing an adverse event Known allergy to the blinded study medications

Ages Eligible for Study
-----------------
Minimum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study will include 4 sessions. Participants will be randomly assigned to the order in which they receive one drug (or combination of drugs) per session at each study visit.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Blinded study medication. This is a within-subject study so all session procedures will be identical. The specific medications administered that study day will be the only change each session. Study days will last approximately 8 hours and will be conducted on an outpatient basis. Participants will be asked to complete standardized pain testing procedures, do brief physical functioning testing, undergo blood draws and complete questionnaires and cognitive testing at multiple points over the course of each study visit. | Drug: Blinded study medication<br>* Blinded study medication: This is a double-blind within-subject Phase II trial. Study medications will remain blinded. Participants may receive a dose of medication from one or more of the following categories: prescription stimulants, prescription benzodiazepines, prescription opioids, prescription cannabinoids, over-the-counter medications or placebo (sugar pill). All subjects will serve as their own control. Study medication administration will be randomized within each participant.<br>* Other names: stimulants, benzodiazepines, opioids, cannabinoids, OTC medications, placebo;|
| Experimental: Arm 2<br>Blinded study medication. Participants will be asked to complete standardized pain testing procedures, do brief physical functioning testing, undergo blood draws and complete questionnaires and cognitive testing at multiple points over the course of each study visit. | Drug: Blinded study medication<br>* Blinded study medication: This is a double-blind within-subject Phase II trial. Study medications will remain blinded. Participants may receive a dose of medication from one or more of the following categories: prescription stimulants, prescription benzodiazepines, prescription opioids, prescription cannabinoids, over-the-counter medications or placebo (sugar pill). All subjects will serve as their own control. Study medication administration will be randomized within each participant.<br>* Other names: stimulants, benzodiazepines, opioids, cannabinoids, OTC medications, placebo;|
| Experimental: Arm 3<br>Blinded study medication. Participants will be asked to complete standardized pain testing procedures, do brief physical functioning testing, undergo blood draws and complete questionnaires and cognitive testing at multiple points over the course of each study visit. | Drug: Blinded study medication<br>* Blinded study medication: This is a double-blind within-subject Phase II trial. Study medications will remain blinded. Participants may receive a dose of medication from one or more of the following categories: prescription stimulants, prescription benzodiazepines, prescription opioids, prescription cannabinoids, over-the-counter medications or placebo (sugar pill). All subjects will serve as their own control. Study medication administration will be randomized within each participant.<br>* Other names: stimulants, benzodiazepines, opioids, cannabinoids, OTC medications, placebo;|
| Experimental: Arm 4<br>Blinded study medication. Participants will be asked to complete standardized pain testing procedures, do brief physical functioning testing, undergo blood draws and complete questionnaires and cognitive testing at multiple points over the course of each study visit. | Drug: Blinded study medication<br>* Blinded study medication: This is a double-blind within-subject Phase II trial. Study medications will remain blinded. Participants may receive a dose of medication from one or more of the following categories: prescription stimulants, prescription benzodiazepines, prescription opioids, prescription cannabinoids, over-the-counter medications or placebo (sugar pill). All subjects will serve as their own control. Study medication administration will be randomized within each participant.<br>* Other names: stimulants, benzodiazepines, opioids, cannabinoids, OTC medications, placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Largest change from baseline on pain rating | The study will measure whether blinded study medications change pain ratings and pain sensitivity on laboratory pain tests. | 8 hour study session | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Clinical Trial, Phase II