Biomarkers for Prediction of Analgesic Efficacy in Knee OA.

NCT05256342 | Completed

• 1 other identifier: 0069-21-RMB
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief 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. 1.To identify psychophysical and neurophysiological biomarkers that can serve as predictors of response to analgesic pain modulating and non-pain modulating drugs.
2. 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.

Conditions

Knee, Osteoarthritis (OA); Biomarkers for Prediction of OA Treatment Efficacy

Outcome Measures

Primary Outcomes (6)

• CPM, a psychophysical parameter for pain inhibition, NPS

  Post vs pre-treatment changes in Conditioned Pain Modulation (CPM)

  up to 2 years

• TS, a psychophysical parameter for pain facilitation, NPS

  Post vs pre-treatment changes in Temporal Summation of pain (TS)

  up to 2 years

• resting-state EEG theta power, microvolts

  Post vs pre-treatment changes in the EEG power within theta band

  up to 2 years

• resting-state EEG alpha power, microvolts

  Post vs pre-treatment changes in the EEG power within alpha band

  up to 2 years

• Clincial pain, VAS

  Post vs pre-treatment changes in VAS

  up to 2 years

• Pain-related disability, numerical scores

  Post vs pre-treatment changes (disability score)

  up to 2 years

Study Arms (2)

Duloxetine

ACTIVE COMPARATOR

Eight weeks treatment, one pill a day. Week 1st - 30 mg a day. Weeks 2nd - 8th - 60 mg a day.

Drug: Duloxetine 60mg

Etoricoxib

ACTIVE COMPARATOR

Eight weeks treatment. 60 mg daily pill ; from the second week adding omeprazol 20 mg daily

Drug: Etoricoxib 60 mg; Drug: omeprazol

Interventions

Duloxetine 60mg DRUG

Eight weeks treatment, one pill daily. 1st week 30mg; weeks 2-7th -- 60 mg daily.

Also known as: Cymbalta

Duloxetine

Etoricoxib 60 mg DRUG

One pill daily for 8 weeks

Also known as: Arcoxia

Etoricoxib

omeprazol DRUG

20 mg daily; will be taken with Etoricoxib from the second week of treatment

Also known as: Prilosec, Losec

Etoricoxib

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rambam Health Care Campus: lead

Study Sites (2)

Rambam Health Care Campus

Haifa, 31096, Israel

Location

Rambam Health Care Campus

Haifa, Israel

Location

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Duloxetine Hydrochloride; Etoricoxib; Omeprazole

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfones; Pyridines; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• David Yarnitsky, Prof

  Rambam Health Care Campus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2021
• First Posted: February 25, 2022
• Study Start: December 30, 2021
• Primary Completion: April 7, 2024
• Study Completion: April 8, 2024
• Last Updated: April 12, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

IL (2)