Knee Osteoarthritis
Conditions
Keywords
Clinical Trial, Phase II
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.
Interventions
DRUGBlinded study medication
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.
Sponsors
National Institute on Drug Abuse (NIDA)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Within-subjects design. Two pills will be administered at each study visit. Participants and study staff will be blind to the drug(s) administered.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Largest Change From Baseline on Clinical Pain Rating | 8 hour study session | The study will measure whether blinded study medications change clinical pain ratings (0-100 pain rating scale). Higher score indicates worse outcome. Biggest difference from baseline over the entire session is reported. |
Countries
United States
Participant flow
Pre-assignment details
Experimental Session 1 is a safety session and completed first. The remaining sessions were completed in triple blinded randomized order.
Participants by arm
| Arm | Count |
|---|---|
| Overall 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.
This is a double-blind within-subject Phase II trial. Study medications will remain blinded. All subjects will serve as their own control. Study medication administration will be randomized within each participant. | 58 |
| Total | 58 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 62.34 years STANDARD_DEVIATION 6.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Region of Enrollment United States | 58 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 58 | 0 / 58 | 0 / 58 | 0 / 58 |
| other Total, other adverse events | 15 / 58 | 10 / 58 | 13 / 58 | 21 / 58 |
| serious Total, serious adverse events | 0 / 58 | 0 / 58 | 0 / 58 | 0 / 58 |
Outcome results
Primary
Largest Change From Baseline on Clinical Pain Rating
The study will measure whether blinded study medications change clinical pain ratings (0-100 pain rating scale). Higher score indicates worse outcome. Biggest difference from baseline over the entire session is reported.
Time frame: 8 hour study session
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Placebo | Largest Change From Baseline on Clinical Pain Rating | Baseline | 24.19 score on a scale | Standard Deviation 23.63 |
| Placebo + Placebo | Largest Change From Baseline on Clinical Pain Rating | Peak Effect | 12.76 score on a scale | Standard Deviation 17.81 |
| Hydromorphone + Placebo | Largest Change From Baseline on Clinical Pain Rating | Peak Effect | 9.40 score on a scale | Standard Deviation 16.27 |
| Hydromorphone + Placebo | Largest Change From Baseline on Clinical Pain Rating | Baseline | 30.48 score on a scale | Standard Deviation 27.39 |
| Dronabinol + Placebo | Largest Change From Baseline on Clinical Pain Rating | Baseline | 28.55 score on a scale | Standard Deviation 26.78 |
| Dronabinol + Placebo | Largest Change From Baseline on Clinical Pain Rating | Peak Effect | 12.80 score on a scale | Standard Deviation 17.5 |
| Hydromorphone + Dronabinol | Largest Change From Baseline on Clinical Pain Rating | Baseline | 26.38 score on a scale | Standard Deviation 25.86 |
| Hydromorphone + Dronabinol | Largest Change From Baseline on Clinical Pain Rating | Peak Effect | 12.41 score on a scale | Standard Deviation 16.92 |
p-value: 0.021ANOVA