Clinical trial NCT05558540: Spinal Cord Stimulation for Intractable Chronic Lower Abdominal Neuropathic Pain Caused by Endometriosis
Official title: Spinal Cord Stimulation for Intractable Chronic Lower Abdominal Neuropathic Pain Caused by Endometriosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Endometriosis
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: Boston Scientific Group
First posted: 2022-09-28
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All women participating in the trial will receive a SCS. Women will first undergo a trial period of 14 days. If succesful (\>50% pain reduction), women will receive a permanently implanted SCS. The follow-up period will enclose 12 months. There is an aimed sample size of 15 participants. However, due to financial limitations, inclusion will stop after 10 women have been succesfully implanted with a permanent SCS.
Primary purpose: TREATMENT

Brief summary: Endometriosis is a chronic, inflammatory disease where endometrium-like tissue is present outside the uterus. Nerve cells in the proximity of this tissue express cytokine receptors causing a signaling cascade. This results in active cross-talk between endometriosis and nerves, causing pelvic pain. Other symptoms associated with endometriosis are cyclical such as dysmenorrhea and dysuria, and non-cyclical such as dyspareunia. Despite adequate disease management, women can still experience endometriosis-related pain. A recent development proven to be efficient in treatment of neuropathic pain, is Spinal Cord Stimulation (SCS). It is also thought to be effective in the treatment of visceral pain. Several studies found Spinal Cord Stimulation (SCS) to be effective in the reduction of endometriosis-related pelvic pain. However, scientific evidence on the efficacy of SCS in visceral pain is limited.

Detailed description: Endometriosis is an estrogen-dependent gynaecologicalcondition characterized by the presence and growth of ectopic endometrial tissue. This tissue stimulates the infiltration of immune cells such as macrophages andmast cells into the peritoneal cavity. Both the immune cells and the endometriotic tissue secrete cytokines which create an inflammatory microenvironment. Nerve cells located in the proximity of endometriosis lesions express cytokine receptors which stimulate a cascade of signalling kinases within the nerve. This results in an active cross-talk between endometriosis and nerves causing endometriosis associated pain.

Because of the chronic nature of endometriosis, treatment can be challenging difficult. It consists of three pillars: hormonal therapy, surgery and conventional pain management. Despite adequate disease management, women with endometriosis can still experience endometriosis-associated chronic pelvic pain. This might suggest that the pathology was either an incidental finding, or that other mechanisms continue to generate pain without the need for a peripheral input. One study proposed that central sensitization may be involved mechanistically in the development and maintenance of endometriosis-related pain. The hypothesis was that persistent nociceptive input from endometriotic tissues might result in increased responsiveness among dorsal horn neurons processing input from the affected viscera and pelvic tissues \[1\].

When standard endometriosis treatment is insufficient in the suppression of endometriosis-related pelvic pain, spinal cord stimulation (SCS), an accepted treatment option for neuropathic pain, could be a potential treatment.This hypothesis was substantiated by several (case) studies. However, they stated that studies on SCS for treatment of visceral pain is limited and made a call for action to broaden this knowledge

Eligibility criteria: Inclusion Criteria:

* Premenopausal woman aged ≥ 18 years
* Patients with endometriosis/ adenomyosis confirmed at surgery macroscopically and without options for further surgical treatment.
* Patients with at least one of the endometriosis related pain symptoms: dysmenorrhea, pelvic pain or dyspareunia. With a mean pain NRS of at least 5 (scale 0-10).
* The pain complaints are therapy resistant (including hormonal, medical and/or surgical options).
* Refractory pain; before neuromodulation patient has tried: Paracetamol, NSAIDs, Anti neuropathic pain therapy, TENS.
* The patient meets all the inclusion criteria for the implantation of a neurostimulation system as typically utilized in the study center.
* Neurologic exam without marked motor deficit.
* Subject has been screened by a multi-disciplinary panel including a psychologist and deemed suitable for implantation
* Subject is able and willing to comply with the follow-up schedule and protocol
* Subject is able to provide written informed consent

Exclusion Criteria:

* Female subject of childbearing potential is pregnant/nursing or plans to become pregnant during the course of the study.
* The presence of malignancy
* Subject currently has an active implantable device including ICD, pacemaker, spinal cord stimulator or intrathecal drug pump
* Subject is unable to operate the device
* Previous Neurostimulation therapy

Primary outcomes:
measure: Change in pain severity at 6 month follow-up
timeFrame: 6 months
Secondary outcomes:
measure: Change in Mean pain from baseline until 12 month follow-up
timeFrame: 12 months
measure: Patient's global impression of change
timeFrame: 12 months
measure: Change in quality of life
timeFrame: 12 months
measure: Change in quality of life
timeFrame: 12 months
measure: Change in fatigue
timeFrame: 12 months
measure: Change in Pain Catastrophizing Scale
timeFrame: 12 months
measure: Change in Central Sensitization Inventory
timeFrame: 12 months
measure: Change in pain medication use
timeFrame: 12 months
measure: Lost working days
timeFrame: 6 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location VUmc
state: Noord Holland
Study officials:
References:
citation: Bajaj P, Bajaj P, Madsen H, Arendt-Nielsen L. Endometriosis is associated with central sensitization: a psychophysical controlled study. J Pain. 2003 Sep;4(7):372-80. doi: 10.1016/s1526-5900(03)00720-x.