Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT02672202 |
| Other study ID # |
614-15-RMB Hernia_CTIL |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
January 12, 2016 |
| Last updated |
September 26, 2017 |
| Start date |
February 2016 |
| Est. completion date |
May 2017 |
Study information
| Verified date |
September 2017 |
| Source |
Rambam Health Care Campus |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
Description:
Background
Pro-nociceptive pain modulation profile (PMP) is characterized by either:
(i) decreased inhibition of pain, i.e.inhibitory pro-nociceptive PMP, (ii) increased
facilitation, i.e. facilitatory pro-nociceptive PMP, or (iii) both, i.e. dual pro-nociceptive
PMP.
The counterpart of pro-nociceptive, i.e., 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 and/or 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, i.e., 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 patient's 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, i.e. 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.
