Novel Non-opioid Post-surgical Pain Treatment in Females

Study Overview
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Brief Summary
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This study aims to determine if treatment with Carbidopa/Levodopa and Naproxen in females (biological sex) with acute pain after a bunionectomy or toe fusion (24hrs, 48hrs and 5 days) will reduce pain when compared with females receiving Placebo and Naproxen.

Detailed Description
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Acute post-surgical pain remains commonly treated with opioids. Although such treatments are efficacious, they can lead to opioid dependency. Disturbingly, opioid abuse often began as a direct consequence of prescription medications, primarily for pain management, and post-surgical pain management. Recent studies in from Apkarian lab suggest that the combination of dopamine and non-steroidal anti-inflammatory may be a safe, tolerable and efficacious novel post-surgical pain treatment option. Therefore, the main hypothesis is: patients treated with Carbidopa/Levodopa and Naproxen will show a statistically significant decrease in post-surgical pain when compared with control intervention (Placebo plus Naproxen (250mg)). This will be done through a double-blind, randomized, placebo-controlled, parallel-group trial of the pharmacological treatment Carbidopa/Levodopa for females (N = 60) undergoing a bunionectomy or toe fusion surgery.

Official Title
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Novel Non-opioid Post-surgical Pain Treatment in Females

Conditions
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Acute Pain, Bunionectomy, Toe Fusion

Intervention / Treatment
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* Drug: Carbidopa-Levodopa (100mg/25mg):
* Drug: Naproxen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: female with no racial or ethnic restrictions; 18 to 75 years old; Have a bunionectomy or toe fusion surgery scheduled; must be able to read, understand, and sign consent form; generally healthy. Exclusion Criteria: Chronic neurologic conditions, e.g., Parkinson's pregnancy; opioids use 60 mg/day oral morphine milligram equivalent.; use of anticoagulants (low dose ASA allowed); history of gastric ulcer; renal insufficiency or congestive heart failure, contraindication to study medication as determined by surgeon Any medical condition that in the investigator's judgment may prevent the individual from completing the study or put the individual at undue risk In the judgment of the investigator, unable or unwilling to follow protocol and instructions; Diagnosis of psychological diseases, such as major depression; bipolar disorder.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carbidopa-Levodopa (100mg/25mg) + Naproxen (250mg)<br>The study drug, Carbidopa-Levodopa, is an FDA-approved medicine traditionally used for the treatment of Parkinson's disease. The study drug will be used for an un-approved or un-labeled use: potentially managing pain in post-surgical patients. Carbidopa/Levodopa is an artificially made version of a naturally occurring hormone that helps regulate brain activity (Levodopa), combined with an artificially made version of a naturally occurring molecule that inhibits the breakdown of Levodopa (Carbidopa). Naproxen (250mg): Participants will receive one capsule TID, throughout the 5 days of the treatment period. Naproxen will be prescribed for active and control group. | Drug: Carbidopa-Levodopa (100mg/25mg):<br>* Participants will take 2 capsules (one containing naproxen, and the other containing either placebo or carbidopa/levodopa) 3 times per day (TID) for 5 days, the first dose is given right after the surgical procedure.<br>* Other names: Rytary;Drug: Naproxen<br>* Participants will take 2 capsules (one containing naproxen, and the other containing either placebo or carbidopa/levodopa) 3 times per day (TID) for 5 days, the first dose is given right after the surgical procedure.<br>* Other names: Menstridol;|
| Placebo Comparator: Placebo + Naproxen (250mg)<br>Placebo:Participants will receive 1 the capsules on a three-times a day schedule for 5 days. A placebo looks like the study drug but is an inactive substance that has no medication. Researchers use a placebo to see if the study drug works better or is safer than not taking anything. Naproxen (250mg): Participants will receive one capsule TID, throughout the 5 days of the treatment period. Naproxen will be prescribed for active and control group. | Drug: Naproxen<br>* Participants will take 2 capsules (one containing naproxen, and the other containing either placebo or carbidopa/levodopa) 3 times per day (TID) for 5 days, the first dose is given right after the surgical procedure.<br>* Other names: Menstridol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-Surgical Pain using Numeric Rating Scale (NRS) | The primary endpoint will be the severity of pain measured by mean post surgical pain from surgery to end of intervention ( 1 week) and end of the study, as indexed by a NRS. The NRS pain scale is a simple 10- point scale (0 = ''no pain'', 10 = ''pain as bad as you can imagine''). Mean pain during treatment will be compared between intervention groups. | 1 and 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Global Impression of Change (PGIC) | This questionnaire reflects a patient's belief about the efficacy of treatment. PGIC is a 7 point scale depicting a patient's rating of overall improvement. PGIC score will be compared between intervention groups. | 1 and 4 weeks | 
| Adverse Events | Participants will be query for possible adverse events during the intervention period ( 1 weeks). Incidence of adverse events will be reported every visit.The frequency and severity of adverse effects will be compared between each intervention group. | 1 and 4 weeks |