Ignite Creation Date:
2024-05-06 @ 8:08 AM
Last Modification Date:
2024-10-26 @ 11:56 AM
Study NCT ID:
NCT02672202
Status:
TERMINATED
Last Update Posted:
2017-09-28
First Post:
2016-01-12
Brief Title:
Shifting Pain Modulation From Pro-to Anti-nociceptive
Sponsor:
Rambam Health Care Campus
Organization:
Rambam Health Care Campus
Study Overview
Official Title:
Shifting Pain Modulation From Pro-to Anti-nociceptive Individualized Prevention of Post Operative Pain
Status:
TERMINATED
Status Verified Date:
2017-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Recruitment rate was slow so we could not complete the study
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To create a data base that will facilitate the enrichment of the insights regarding post-operative pain development and to identify those individuals with the potential to develop this kind of pain The identification will be based on the individualized pain modulation profile composed of a battery of tests as detailed below
Detailed Description:
Background
Pro-nociceptive pain modulation profile PMP is characterized by either
i decreased inhibition of pain ieinhibitory pro-nociceptive PMP ii increased facilitation ie facilitatory pro-nociceptive PMP or iii both ie dual pro-nociceptive PMP
The counterpart of pro-nociceptive ie anti-nociceptive PMP has not yet been explored The investigators expect individuals harboring this profile to be at lower risk for pain acquisition and experience less intense pain Pain modulation is commonly altered in pain patients toward a pro-nociceptive pain modulation profile PMP expressed in the lab by increased facilitation andor decreased inhibition of experimental pain and clinically by high pain phenotype
The proposed study seeks to explore the yet to be characterized mirror image of pro-nociception ie the situation where individuals exhibit reduced pain facilitation and more efficient pain inhibition This domain of anti-nociceptive PMP is a potential platform for improving pain therapy and prevention Extrapolating from the clinical picture of pro-nociception it is likely that antinociceptive individuals will express a lower pain phenotype with less frequent and less intense pain experiences lower risk of acquiring pain after surgery or trauma and possibly better response to analgesics The investigators would like to explore whether it is possible to shift pain modulation towards anti-nociception in order to obtain the possible benefits of this modulation profile in pain-prone situations
The clinical model the investigators propose for addressing the hypotheses is preemptive drug treatment for reduction of postoperative pain Our specific choice of surgery is inguinal herniorraphy In addition to acute post-operative pain this operation carries a relatively high rate of chronic post-operative pain ranging from 10 to 54 of patients with most reports indicating towards the lower end of this range
Our specific aims are to explore in the setup of post operative pain after inguinal herniorraphy the shift of PMP from pro- towards anti-nociceptive based on each of the following testing domains
i Psychophysical and neurophysiological data describing facilitatory and inhibitory modulation capacity of the patient
ii Psychological data describing patients behavior such as catastrophizing anxiety and depression pain sensitivity and life orientation
iii Blood tests to evaluate Micro RNA which regulate downstream transcription or shutting down gene expression in order to evaluate their role as predictor for evolving chronic pain and v individual case data related to age gender education socioeconomic parameters and personal medical history
Subjects
Study A One hundred and forty healthy subjects range 20-79 20 subjects per age decade 10 M and 10 F will participate in the first phase of the study aimed to collect normative data from healthy population
Study B Two hundred and twenty patients range 18-75 scheduled for inguinal herniorraphy will be enrolled
Study design Study I - Normative data collection for the inhibitory and excitatory pain modulation responses a study on healthy subjects
The study will include one session In this session after signing informed consent subjects will
i fill out state of health questionnaire ii record 5 minutes of resting state EEG and iii undergo a short familiarization with the various stimulation modalities
Thereafter and along the session subjects will fill the pain related personality questionnaires anxiety and depression catastrophizing pain sensitivity life orientation test and ten item personality measure followed by psychophysical assessments which will include assessment of conditioned pain modulation CPM and temporal pain summation TS as described later on A sample of 20 ml of blood will be drawn from all subjects at the end of the session
Study II - Herniorraphy surgery patients This study is a randomized placebo-controlled double-blind three parallel arms non-crossover longitudinal study in four groups of patients identified by their PMPs The study will consist of two assessment sessions the first between 1 to 2 weeks before surgery and the second 3 month after surgery The sessions will be conducted by experienced experimenter and will include the same psychophysical and psychological assessments as in Study I after signing informed consent patients will undergo a short familiarization with the various stimulation modalities and then undergo the various stimuli
At the end of this session patients will be assigned into one of four groups
i dual pro-nociceptive ii inhibitory pro-nociceptive iii facilitatory pro-nociceptive and iv anti-nociceptive
45 patients will be assigned into each group by order of their recruitment Third of the patients in each group will be randomized to Duloxetine DUL third to Pregabalin PGB and the other third to Placebo PLA Each group will receive two treatment doses of the drug before surgery ie one in the evening before and one at the morning of the surgery Patients will then undergo surgery to be performed by one team of surgeons under a standardized protocol of general anesthesia After surgery patients will be treated by a standardized analgesic protocol until discharge normally the morning after surgery Acute pain intensity and analgesics consumption during the first 24 hours will be recorded On post-operative day POD 1 patients will fill a patient outcome questionnaire that will include information about their perceived post-operative pain intensity and the extent of pain interference with activities and effects on mood and anxiety A periodic phone call for chronic postoperative pain will be pursued at 1 2 4 weeks and 6 months after surgery An experimenter blinded to the psycho-physical group assignment will follow the pain state after surgery
Two samples of 20 ml of blood will be drawn from all patients first blood withdrawal will be done before surgery and the second at a clinic visit between 3 and 6 month after surgery
Pro-nociceptive pain modulation profile PMP is characterized by either
i decreased inhibition of pain ieinhibitory pro-nociceptive PMP ii increased facilitation ie facilitatory pro-nociceptive PMP or iii both ie dual pro-nociceptive PMP
The counterpart of pro-nociceptive ie anti-nociceptive PMP has not yet been explored The investigators expect individuals harboring this profile to be at lower risk for pain acquisition and experience less intense pain Pain modulation is commonly altered in pain patients toward a pro-nociceptive pain modulation profile PMP expressed in the lab by increased facilitation andor decreased inhibition of experimental pain and clinically by high pain phenotype
The proposed study seeks to explore the yet to be characterized mirror image of pro-nociception ie the situation where individuals exhibit reduced pain facilitation and more efficient pain inhibition This domain of anti-nociceptive PMP is a potential platform for improving pain therapy and prevention Extrapolating from the clinical picture of pro-nociception it is likely that antinociceptive individuals will express a lower pain phenotype with less frequent and less intense pain experiences lower risk of acquiring pain after surgery or trauma and possibly better response to analgesics The investigators would like to explore whether it is possible to shift pain modulation towards anti-nociception in order to obtain the possible benefits of this modulation profile in pain-prone situations
The clinical model the investigators propose for addressing the hypotheses is preemptive drug treatment for reduction of postoperative pain Our specific choice of surgery is inguinal herniorraphy In addition to acute post-operative pain this operation carries a relatively high rate of chronic post-operative pain ranging from 10 to 54 of patients with most reports indicating towards the lower end of this range
Our specific aims are to explore in the setup of post operative pain after inguinal herniorraphy the shift of PMP from pro- towards anti-nociceptive based on each of the following testing domains
i Psychophysical and neurophysiological data describing facilitatory and inhibitory modulation capacity of the patient
ii Psychological data describing patients behavior such as catastrophizing anxiety and depression pain sensitivity and life orientation
iii Blood tests to evaluate Micro RNA which regulate downstream transcription or shutting down gene expression in order to evaluate their role as predictor for evolving chronic pain and v individual case data related to age gender education socioeconomic parameters and personal medical history
Subjects
Study A One hundred and forty healthy subjects range 20-79 20 subjects per age decade 10 M and 10 F will participate in the first phase of the study aimed to collect normative data from healthy population
Study B Two hundred and twenty patients range 18-75 scheduled for inguinal herniorraphy will be enrolled
Study design Study I - Normative data collection for the inhibitory and excitatory pain modulation responses a study on healthy subjects
The study will include one session In this session after signing informed consent subjects will
i fill out state of health questionnaire ii record 5 minutes of resting state EEG and iii undergo a short familiarization with the various stimulation modalities
Thereafter and along the session subjects will fill the pain related personality questionnaires anxiety and depression catastrophizing pain sensitivity life orientation test and ten item personality measure followed by psychophysical assessments which will include assessment of conditioned pain modulation CPM and temporal pain summation TS as described later on A sample of 20 ml of blood will be drawn from all subjects at the end of the session
Study II - Herniorraphy surgery patients This study is a randomized placebo-controlled double-blind three parallel arms non-crossover longitudinal study in four groups of patients identified by their PMPs The study will consist of two assessment sessions the first between 1 to 2 weeks before surgery and the second 3 month after surgery The sessions will be conducted by experienced experimenter and will include the same psychophysical and psychological assessments as in Study I after signing informed consent patients will undergo a short familiarization with the various stimulation modalities and then undergo the various stimuli
At the end of this session patients will be assigned into one of four groups
i dual pro-nociceptive ii inhibitory pro-nociceptive iii facilitatory pro-nociceptive and iv anti-nociceptive
45 patients will be assigned into each group by order of their recruitment Third of the patients in each group will be randomized to Duloxetine DUL third to Pregabalin PGB and the other third to Placebo PLA Each group will receive two treatment doses of the drug before surgery ie one in the evening before and one at the morning of the surgery Patients will then undergo surgery to be performed by one team of surgeons under a standardized protocol of general anesthesia After surgery patients will be treated by a standardized analgesic protocol until discharge normally the morning after surgery Acute pain intensity and analgesics consumption during the first 24 hours will be recorded On post-operative day POD 1 patients will fill a patient outcome questionnaire that will include information about their perceived post-operative pain intensity and the extent of pain interference with activities and effects on mood and anxiety A periodic phone call for chronic postoperative pain will be pursued at 1 2 4 weeks and 6 months after surgery An experimenter blinded to the psycho-physical group assignment will follow the pain state after surgery
Two samples of 20 ml of blood will be drawn from all patients first blood withdrawal will be done before surgery and the second at a clinic visit between 3 and 6 month after surgery
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None