Biomarkers for Prediction of Analgesic Efficacy in Knee OA.

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

With high NNTs for indiscriminative use in chronic pain, treatment unavoidably entails frustrating long trial and errors. It is timely to identify biomarkers that can predict analgesic efficacy for the individual patient.

The investigators propose a framework of interrelations between patient's pain modulation profile (PMP) and the drug's mode of action (MOA) based on two principles: (1) 'fix the dysfunction', relevant for drugs whose main mode of action is to modulate central pain processing; the more the dysfunctional the better the modulating drug efficacy. For example, patients with pro-nociceptive PMP due to reduced endogenous pain inhibition, as expressed by less efficient CPM will benefit from drugs that fix this dysfunction such as SNRIs, relative to patients whose pain inhibitory capacity is well functioning. Thus, for the modulating drugs, pro-nociceptivity predicts better efficacy. (2) 'bear with the dysfunction', relevant for drugs which are mostly non-modulating, acting mainly in the periphery; the more dysfunctionalת the less the non-modulating drug efficacy. This is since efficacy is limited by the dysfunctional modulation system, despite the drug's MOA-like reduction of peripheral pain mediators. Thus, for the non-modulating drugs, for example NSAIDs, pro-nociceptivity predicts less good efficacy. The likely protocol suggests that patients with anti-nociceptive PMP should be treated primarily by non-modulating drugs, while pro-nociceptive ones should be given modulating drugs.

EEG is an additional source of relevant data on brain pain processing. Being objective and stable along time, EEG based parameters are, thus, very attractive candidates to be useful biomarkers for prediction of analgesia efficacy.

This study will focus on the patients with painful knee osteoarthritis.

The aims of this study are:

1. To identify psychophysical and neurophysiological biomarkers that can serve as predictors of response to analgesic pain modulating and non-pain modulating drugs.

2. To establish a conceptual framework of individualized pain therapy based on inter-relations between patient's parameters of pain modulation and drugs' mode of action.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rambam Health Care Campus
• Treatments: Duloxetine Hydrochloride; Etoricoxib

Criteria

Inclusion Criteria:

• males and females

• ages 45 to 75

• radiographic representation of osteoarthritis of the knee

• minimal or moderate OA severity, based on the Kellgren and Lawrence system classification (1-3)

• knee OA pain for more than 3 months, assessed by the patients as being at level 4/10 and above on average at routine daily standing/walking activities during the last week, without medication

Exclusion Criteria:

• other more prominent pain

• previous bilateral total knee replacement (TKR) surgery

• secondary OA (post-traumatic or post-infectious, osteochondritis dissecans (OCD) and enteropathic arthritis (EA) deformity)

• significant additional health problems such as substantial painful neuropathy, diabetes above of 5 yrs, renal failure, congestive heart failure, neurological diseases that might mask the pain processing system or reduce patient's cooperation or report capabilities, and significant psychiatric disorders

• use of opioids or cannabis

• known diseases of gastrointestinal tract such as esophagitis, gastritis and duodenitis

• patients that had side effects to the study drugs in the past.