Ignite Creation Date:
2024-05-06 @ 5:17 PM
Last Modification Date:
2024-10-26 @ 2:25 PM
Study NCT ID:
NCT05256342
Status:
COMPLETED
Last Update Posted:
2024-04-12
First Post:
2021-05-19
Brief Title:
Biomarkers for Prediction of Analgesic Efficacy in Knee OA
Sponsor:
Rambam Health Care Campus
Organization:
Rambam Health Care Campus
Study Overview
Official Title:
Biomarkers for Prediction of Analgesic Efficacy Based on Interrelations Between Pain Modulation and EEG vs Drugs Mode of Action in Knee OA
Status:
COMPLETED
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 patients pain modulation profile PMP and the drugs 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 drugs 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 patients parameters of pain modulation and drugs mode of action
The investigators propose a framework of interrelations between patients pain modulation profile PMP and the drugs 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 drugs 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 patients parameters of pain modulation and drugs mode of action
Detailed Description:
Study design
The study design includes two experimental meeting sessions before and at the end after the treatment which include clinical and experimental assessments After the first experimental session the patients will be asked to rate twice a week their daily pain along two weeks in order to confirm their OA pain level the patients with the mean pain score of 4 will be supplied with the study medications Along the 8 weeks-long treatment period they will provide the rating of OA pain subjective estimation of pain alleviation and reports of side effects
Clinical assessment Will be performed by the study physician The data on OA severity by Kellgren and Lawrence system classification range of motion and current OA pain last 48 h will be collected In addition all patients will fill the brief pain inventory questioner BPI to assess their pain characteristics In addition all patients will be tested for the Western Ontario and McMaster Universities Osteoarthritis Index WOMAC for assessment of OA pain stiffness and physical function
Experimental session
1 At the beginning of pre-treatment experimental session all patients will fill a following set of psychological pain-related questioners organized in one document 1 pain catastrophizing scale PCS 2 HADS anxiety and depression 3 short-form health survey SF-12 5 pain sensitivity questionnaire PSQ In addition basic assessment of psychomotor attention and cognitive functioning will be performed using 6 Trial making tests A and B TMT A and B and 7 Digits symbol substitution test DSST All the data will be coded and no personal data will be exposed
2 Resting-state EEG recording Three minutes of resting-state EEG eyes closed will be recorded using the 64-channel EEG recording Brain Products GmbH Munich Germany
3 Psychophysical pain assessment All tests will be performed remotely from the painful area - on arm or hand The following tests will be performed
Electrical and mechanical temporal summation TS For the assessment of electrical TS a train of 10 electrical stimuli Digitimer DS7A Digitimer Ltd WelWyn Garden City England of 2 msec width will be delivered to the non-dominant forearm with ISI of 1 sec Subject will rate the perceived pain after the 1st and after the 5th stimuli using verbal numerical rating scale NRS Mechanical TS with be assessed using ten application of 256mN dull needle from the DFNS set for quantitative sensory assessment aimed to evoke slight pricking sensation The TS responses will be calculated as a difference of the perceived pain between last vs first pain score
CPM A combination of tonic heat stimulus up to 50oC duration up to 20 sec TSA Medoc Israel and of 3 pressure pain threshold PPT measurements performed on the dominant trapezius Algomed Medoc Israel 3-sec inter-stimulus interval ISI will be given Stimulus heat intensity will be individually adjusted to induce pain at intensity of 50 on 0 - 100 numerical rating scale NRS These stimuli will be delivered to the dominant forearm serving a test-stimulus After a 10 min break the non-dominant hand will be immersed into cold water bath for a period of 60-70 sec 4-10 deg After 10 sec of the immersion the test-stimulus will be delivered again while the hand is still in the water Along all stimulation period the subjects will rate their pain perception using numerical pain scale A CPM response will be calculated as a difference in the pain perception to the test-stimulus during the immersion as compared to the test-stimulus given stand-alone
Treatment follow-up
Phone follow-up will be performed weekly reports at weeks 1-2 and 5-6 twice a week for weeks 3-4 and 7-8 The patients will provide their OA pain score rating of the pain-relieving drug effect 0-100 scale and describe the treatment-related side effects for the period of last 48 hours
Statistical analysis
The classical statistical analysis will be based on correlations between PMP and degree of drug efficacy represented by percentage pain reduction We then construct 3 independent model systems one for each of the 3 PMP parameters CPM TS and EEG based connectivity Within each model we first test the two correlations under the presumed pain modulating and non-modulating drugs between PMP and drug efficacy A machine learning-based cross-validation and permutation tests will be used in order to access generalizability and statistical significance of the of the findings
The study design includes two experimental meeting sessions before and at the end after the treatment which include clinical and experimental assessments After the first experimental session the patients will be asked to rate twice a week their daily pain along two weeks in order to confirm their OA pain level the patients with the mean pain score of 4 will be supplied with the study medications Along the 8 weeks-long treatment period they will provide the rating of OA pain subjective estimation of pain alleviation and reports of side effects
Clinical assessment Will be performed by the study physician The data on OA severity by Kellgren and Lawrence system classification range of motion and current OA pain last 48 h will be collected In addition all patients will fill the brief pain inventory questioner BPI to assess their pain characteristics In addition all patients will be tested for the Western Ontario and McMaster Universities Osteoarthritis Index WOMAC for assessment of OA pain stiffness and physical function
Experimental session
1 At the beginning of pre-treatment experimental session all patients will fill a following set of psychological pain-related questioners organized in one document 1 pain catastrophizing scale PCS 2 HADS anxiety and depression 3 short-form health survey SF-12 5 pain sensitivity questionnaire PSQ In addition basic assessment of psychomotor attention and cognitive functioning will be performed using 6 Trial making tests A and B TMT A and B and 7 Digits symbol substitution test DSST All the data will be coded and no personal data will be exposed
2 Resting-state EEG recording Three minutes of resting-state EEG eyes closed will be recorded using the 64-channel EEG recording Brain Products GmbH Munich Germany
3 Psychophysical pain assessment All tests will be performed remotely from the painful area - on arm or hand The following tests will be performed
Electrical and mechanical temporal summation TS For the assessment of electrical TS a train of 10 electrical stimuli Digitimer DS7A Digitimer Ltd WelWyn Garden City England of 2 msec width will be delivered to the non-dominant forearm with ISI of 1 sec Subject will rate the perceived pain after the 1st and after the 5th stimuli using verbal numerical rating scale NRS Mechanical TS with be assessed using ten application of 256mN dull needle from the DFNS set for quantitative sensory assessment aimed to evoke slight pricking sensation The TS responses will be calculated as a difference of the perceived pain between last vs first pain score
CPM A combination of tonic heat stimulus up to 50oC duration up to 20 sec TSA Medoc Israel and of 3 pressure pain threshold PPT measurements performed on the dominant trapezius Algomed Medoc Israel 3-sec inter-stimulus interval ISI will be given Stimulus heat intensity will be individually adjusted to induce pain at intensity of 50 on 0 - 100 numerical rating scale NRS These stimuli will be delivered to the dominant forearm serving a test-stimulus After a 10 min break the non-dominant hand will be immersed into cold water bath for a period of 60-70 sec 4-10 deg After 10 sec of the immersion the test-stimulus will be delivered again while the hand is still in the water Along all stimulation period the subjects will rate their pain perception using numerical pain scale A CPM response will be calculated as a difference in the pain perception to the test-stimulus during the immersion as compared to the test-stimulus given stand-alone
Treatment follow-up
Phone follow-up will be performed weekly reports at weeks 1-2 and 5-6 twice a week for weeks 3-4 and 7-8 The patients will provide their OA pain score rating of the pain-relieving drug effect 0-100 scale and describe the treatment-related side effects for the period of last 48 hours
Statistical analysis
The classical statistical analysis will be based on correlations between PMP and degree of drug efficacy represented by percentage pain reduction We then construct 3 independent model systems one for each of the 3 PMP parameters CPM TS and EEG based connectivity Within each model we first test the two correlations under the presumed pain modulating and non-modulating drugs between PMP and drug efficacy A machine learning-based cross-validation and permutation tests will be used in order to access generalizability and statistical significance of the of the findings
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None