Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05949554 |
| Other study ID # |
APHP230352 |
| Secondary ID |
2023-A00080-45 |
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 2023 |
| Est. completion date |
October 2024 |
Study information
| Verified date |
July 2023 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
Joaquim MATEO, MD |
| Phone |
1 49 95 83 74 |
| Email |
joaquim.mateo[@]aphp.fr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Chronic pain symptoms can lead to sleep and mood disorders, restrict domestic and work
activities and have a significant impact on quality of life. The prevalence of chronic pain
in the general population varies between 10 and 52% depending on the study, 7% of which is
neuropathic pain.
Anxiety-depression comorbidities are found in a large number of patients, with harmful
consequences on pain since they exacerbate symptoms and their repercussions. Conversely, pain
increases psychological distress.
Ketamine has been used in the context of depressive episodes for its rapid action. It is also
increasingly used in chronic pain due to its ability to regulate the "wind-up" effect, a
phenomenon involved in the central hypersensitization that is inevitably present in
neuropathic pain of prolonged duration.
Several studies have found electroencephalographic (EEG) signatures associated with a good
antidepressant response to Ketamine. The frequency, absolute and relative power and cordance
of the EEG signal in certain frequency ranges (theta, alpha, beta and gamma) could be useful
to guide and adapt therapies for depression and pain.
Description:
The prevalence of chronic pain in the general population varies between 10 and 52% depending
on the study, 7% of which is neuropathic pain. These neuropathic pains have various origins:
post-surgical, post-herpetic, post-traumatic, etc. These chronic pain symptoms can lead to
sleep and mood disorders, restrict domestic and work activities and have a significant impact
on quality of life.
Anxiety-depression comorbidities are found in a large number of patients, with harmful
consequences on pain since they aggravate symptoms and their repercussions. Conversely, pain
increases psychological distress.
Ketamine, derived from phencyclidine, is an anesthetic agent used since the 1960s. It acts by
non-competitive antagonism of the N-methyl-D-aspartate (NMDA) receptors found mainly in the
hippocampus and prefrontal cortex. This receptor is one of the binding sites for glutamate,
an excitatory neurotransmitter involved in the transmission of painful messages, long-term
memory processes, and hyperalgesia. Ketamine has been used in the context of depressive
episodes characterized by its rapid action. It is also increasingly used in chronic pain due
to its regulating action on the "wind up" effect, a phenomenon involved in the central
hypersensitization that is inevitably present in neuropathic pain with a prolonged course.
The mechanisms underlying the improvement of neuropathic pain after ketamine infusion are not
fully elucidated. Some animal studies suggest a prolonged anti-aversive effect on the
anterior cingulate cortex or a weaker connectivity between the prefrontal cortex and the
precuneus in patients who respond to ketamine. At the same time, the antidepressant effect
seems to be linked to an action on the prefrontal cortex. Overall, the literature shows a
strong association between anxiety-depressive symptoms and chronic pain.
EEG recording of patients with neuropathic pain before and during ketamine infusion would
allow the acquisition of important electro-physiological data.
Several studies have found that EEG signatures was associated with a good antidepressant
response to Ketamine. The frequency, absolute and relative power and cordance of the EEG
signal in certain frequency ranges (theta, alpha, beta and gamma) could be useful for guiding
and adapting therapies for depression as well as pain.
Patients over 18 years old are eligible to participate in this protocol. At the time of the
pain follow-up consultation, they will be given a letter of information on the objectives and
progress of the study. Their non-opposition to participate in this study will be collected at
the time of their entry into the department as part of their scheduled hospitalization.
The protocol will start during a scheduled hospitalization to administer the first Ketamine
infusion.
The protocol does not interact with the care procedure.
- During their hospitalization, the participants would have to complete of a concise pain
questionnaire and Hospital Anxiety and Depression scale (HAD score).
Before Ketamine infusions at week 1 (W1) and week 3 (W3), concise pain questionnaire, HAD
score, Pain Catastrophizing Scale (PCS score), and the Montreal Cognitive assessment (MoCA
test) are performed. Then, an EEG is recorded for about 60 minutes using a noninvasive device
(Masimo ©).
The study physician collecting the data was not involved in the patient's management at any
time. The measures cannot influence the prescribing physician since at this stage the data
are not yet analyzed and available.
No added risk.
Continuous data will be expressed as median [interquartile] and categorical data as n (%).
Categorical variables will be compared by Mann-Whitney test and continuous variables by
Wilcoxon test.
The correlation between pain, anxiety-depressive symptoms and catastrophizing will be
estimated by Pearson correlation test.
The ability of the various EEG parameters of interest to predict the occurrence of an
improvement in pain will be estimated by constructing a ROC curve. The area of these ROC
curves will be measured, and the corresponding 95% confidence interval estimated. The areas
under the ROC curve of the different parameters will be compared by DeLong test.
The statistical analysis will be carried out using the statistical analysis software " R "
(The R Foundation, Vienna, Austria) under the responsibility of Pr Etienne GAYAT.
