EndometriosisPhase 3EASYlightNCT06161805
Esketamine as Treatment for Chronic Pain Due to Endometriosis: a RCT Study
A Phase 3 study testing Esketamine hydrochloride in people with Endometriosis and Chronic Pelvic Pain Syndrome, run by Reinier de Graaf Groep at 1 site in Netherlands.
Trial summary
The goal of this randomized controlled trial is to investigate the effect of esketamine versus placebo on the NRS score for chronic pelvic pain. Secondary endpoints are to assess pain scores, side-effects, quality of life, depressive symptoms and pain coping. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Endometriosis, Chronic Pelvic Pain Syndrome
- What is being tested?
- Esketamine hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Mar 2024to 1 Jun 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women
- All pre-menopausal women aged above 18 years
- Diagnosed with endometriosis (ultrasound, MRI or previous laparoscopic and/or diagnostic surgery) according to the #Enzian classification [52]. This means that endometriosis is present in the following compartments:
- Rectovaginal space (minimal A1) and/or
- Sacrouterine ligaments, cardinal ligaments, pelvic sidewall (minimal B1) and/or
- Rectum (minimal C1) and/or
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- Endometriosis of the intestines, diaphragm and/or
- Adenomyosis (according to the morphological uterus sonographic assessment (MUSA) or evident adenomyosis on the MRI) [53, 54] and/or
- Peritoneal / superficial endometriosis (diagnosed laparoscopically and not treated during surgery).
- Mild to severe chronic pelvic pain (NRS scale >= 6). The 11-point NRS scale ranges from '0' representing no pain to '10' representing the worst pain imaginable.
- Resistant to current recommended lines of analgesics (paracetamol, NSAIDs)
- Usage of strong opioids must not have been prescribed or otherwise have been discontinued for more than 1 week.
- An indication for endometriosis resection surgery or on the waiting list for surgical treatment
- Ability to understand the patient information letter and to give oral and written informed consent
- No alteration in the utilization of hormonal therapy ≤1 months prior to inclusion.
Who cannot join
- Pain score <6 out of 10 (NRS) for chronic pelvic pain
- Endometriosis affecting the bladder and ureter
- Increased intracranial pressure
- Poorly regulated hypertension, >180/100mmHg at rest
- Patients with thyroid disease
- Patients with cancer
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- History of psychiatric illness (schizophrenia, psychosis, delirium, manic depression)
- Serious medical disease (e.g., cardiovascular, renal , pulmonary or liver disease)
- Severe liver disease
- Patients with glaucoma
- Usage of strong opioid medication
- Usage of xanthine derivatives or ergometrine
- Unstable angina, heart failure, history of cerebral vascular accident (CVA)
- Patients suffering from an active infection
- Patients with epilepsy
- Patients trying to achieve pregnancy and or patients who are breastfeeding
- Not being able to answer questionnaires (in Dutch)
- Mentally incompetent (patients not able to make decisions that are in their best interests, this will be evaluated by their treating physician (e.g. patients with an intellectual disability or mental retardation))
- Alcohol or drug abuse
- Patient with a known (es)ketamine allergy
- Abnormal liver enzyme levels at baseline (ASAT, ALAT, GGT, AF, Bilirubin total)
- Patients are allowed to continue the following pain medications: paracetamol, non-steroidal anti-inflammatory drugs as described previously by Sigtermans et al. (Trial NL466 (NTR507)) according to their stable use in dose and frequency.
- in case of tramadol, amitriptylin, selective serotonin reuptake-inhibitors, gabapentin and pregabalin, the usage may also be continued during this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Nederlandse Endometriose Kliniek, Reinier de Graaf Gasthuis
Delft
About this study
The goal of this randomized controlled trial is to investigate the effect of esketamine versus placebo on the NRS score for chronic pelvic pain. Secondary endpoints are to assess pain scores, side-effects, quality of life, depressive symptoms and pain coping.
Read the detailed description
Endometriosis is a chronic inflammatory disease affecting approximately 10% of reproductive-aged women. Severe pain symptoms and subfertility result in a lower quality of life, higher prevalence of depression and loss of productivity. Consequently, the economic impact of endometriosis is high. Treatment options to suppress chronic pain symptoms in patients with (deep) endometriosis are inadequate, resulting in increased opioid consumption. Ketamine (in our study we will use the S-enantiomer, esketamine), is a versatile drug with analgesic, anti-inflammatory and antidepressant effects and is commonly used in the treatment of chronic pain patients and has shown promising outcomes. However, whilst esketamine targets multiple aspects of endometriosis simultaneously (pain, inflammation, depression), studies on esketamine as treatment for chronic pain due to endometriosis have never been reported. Therefore we aim to conduct a randomized controlled trial to assess the efficacy of esketamine infusion versus placebo in the treatment of chronic endometriosis-induced pain.
- Conditions
- Endometriosis, Chronic Pelvic Pain Syndrome
- Being tested
- Esketamine hydrochloride, Placebo
- Medical subject headings
- Endometriosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Esketamine hydrochlorideDrug
Also called ketanest
Esketamine dosing regimen is set at 0.1 mg/kg/h as starting dosage. Dosage will be gradually increased based on heart rate, oxygen saturation, blood pressure and side effects (e.g. nausea and dissociative effects) during a period of 8 hours to a maximum of 0.5 mg/kg/h (in steps of 0.1-0.3-0.5 mg/kg/hour). This dosage regimen is similar to that used earlier by Sigtermans et al. [1].
PlaceboDrug
8 hour infusion with saline (NaCl 0.9%)
| Study group | Role | What they receive |
|---|---|---|
| Esketamine | Experimental | Esketamine dosing regimen is set at 0.1 mg/kg/h as starting dosage. Dosage will be gradually increased based on heart rate, oxygen saturation, blood pressure and side effects (e.g. nausea and dissociative effects) during a period of 8 hours to a maximum of 0.5 mg/kg/h (in steps of 0.1-0.3-0.5 mg/kg/hour). Receives: Drug: Esketamine hydrochloride |
| Placebo | Placebo comparator | 8 hours infusion with saline (NaCl 0.9%) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Chronic pelvic pain
The effect of treatment allocation on the NRS score for chronic pelvic pain. The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Measured: 4 weeks after the 8 hour infusion treatment.
Secondary outcomes (14)
Dysmenorrhea
NRS score for dysmenorrhea. The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Measured: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Dyschezia
NRS scores for dyschezia.The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Measured: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Dysuria
NRS scores for dysuria. The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Measured: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Dyspareunia
NRS score for dyspareunia. The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Measured: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Chronic pelvic pain
NRS score for chronic pelvic pain. The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Measured: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Depressive symptoms
Hospital Anxiety and Depression scale, 14 questions, scale from 0-3, higher scores mean worse outcome.
Measured: Baseline, 4 weeks after infusion treatment
Endometriosis associated Quality of Life
Endometriosis Health Profile-30 (EHP-30). The overall EHP-30 score ranges from 0 to 100, with a high score indicating poorer health-related quality of life.
Measured: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Quality of life in general
EuroQql five-dimensional 5 levels (EQ-5D-5L). According to the Dutch scoring algorithm, the EQ-5D-5L score index value ranges from -0.446 (55555 worst health state) to 1 (11111, best health state).
Measured: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Quality of life in general
EuroQql Visual Analog Scale (EQ-VAS). Overall health will be represented by the EQ-VAS, ranging from 0 to 100, with higher scores indicating better health.
Measured: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Productivity costs
Adjusted productivity costs questionnaire (iPCQ): institute for Medical Technology Assessment (iMTA). Adjusted medical consumption questionnaire: iMTA. Productivity costs will be measured by calculating absence from paid work (absenteeism), reduced productivity at paid work (presenteeism), and productivity loss in unpaid work. Hours of productivity loss will be translated by a standard cost price of productivity per hour.
Measured: 12 weeks post-infusion treatment
Medical costs
Medical consumption costs will be calculated based upon the iMCQ.
Measured: Baseline, 12 weeks post-infusion treatment
Pain coping and cognition
Pain Coping and Cognition list (PCCL), consists of 42 items divided in four scales: pain catastrophising (higher scores mean a higher degree of catastrophising), pain coping (lower scores mean a lower degree of pain coping), internal pain control (lower scores mean less internal pain control) and external pain control (higher scores mean less external pain control.
Measured: Baseline, 12 weeks post-infusion treatment
The effect infusion treatment psychedelic effects
Bowdle questionnaire, scale from 0-100, higher scores mean worse outcome.
Measured: On the day of infusion (prior to infusion and during infusion)
Treatment experience
1 question, treatment rating on a scale from 0 (worst experience possible) -10 (excellent experience)
Measured: Directly after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2023
- Study start1 Mar 2024
- Primary completion1 Jan 2026 (estimated)
- Study completion1 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for EndometriosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1:1 randomization
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Reinier de Graaf Groep
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06161805
- Sponsor's protocol ID
- EASYlight-NEK
- Acronym
- EASYlight
- Status last verified
- Apr 2025
- First submitted
- 23 Oct 2023
- Last updated
- 11 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: upon request
Publications
Sigtermans MJ, van Hilten JJ, Bauer MCR, Arbous SM, Marinus J, Sarton EY, Dahan A. Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1. Pain. 2009 Oct;145(3):304-311. doi: 10.1016/j.pain.2009.06.023. Epub 2009 Jul 14.
PubMed 19604642
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Esketamine as Treatment for Chronic Pain Due to Endometriosis: a RCT Study
- ClinicalTrials.gov ID
- NCT06161805
- Acronym / sponsor ID
- EASYlight / EASYlight-NEK
- Conditions
- Endometriosis, Chronic Pelvic Pain Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Reinier de Graaf GroepUniversity, hospital or other
- Study start
- 1 Mar 2024 (actual)
- Primary completion
- 1 Jan 2026 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 8 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this randomized controlled trial is to investigate the effect of esketamine versus placebo on the NRS score for chronic pelvic pain. Secondary endpoints are to assess pain scores, side-effects, quality of life, depressive symptoms and pain coping.
Detailed description
Endometriosis is a chronic inflammatory disease affecting approximately 10% of reproductive-aged women. Severe pain symptoms and subfertility result in a lower quality of life, higher prevalence of depression and loss of productivity. Consequently, the economic impact of endometriosis is high. Treatment options to suppress chronic pain symptoms in patients with (deep) endometriosis are inadequate, resulting in increased opioid consumption. Ketamine (in our study we will use the S-enantiomer, esketamine), is a versatile drug with analgesic, anti-inflammatory and antidepressant effects and is commonly used in the treatment of chronic pain patients and has shown promising outcomes. However, whilst esketamine targets multiple aspects of endometriosis simultaneously (pain, inflammation, depression), studies on esketamine as treatment for chronic pain due to endometriosis have never been reported. Therefore we aim to conduct a randomized controlled trial to assess the efficacy of esketamine infusion versus placebo in the treatment of chronic endometriosis-induced pain.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 1:1 randomization
| Arm | Type | Receives |
|---|---|---|
| Esketamine | Experimental | Drug: Esketamine hydrochlorideEsketamine dosing regimen is set at 0.1 mg/kg/h as starting dosage. Dosage will be gradually increased based on heart rate, oxygen saturation, blood pressure and side effects (e.g. nausea and dissociative effects) during a period of 8 hours to a maximum of 0.5 mg/kg/h (in steps of 0.1-0.3-0.5 mg/kg/hour). |
| Placebo | Placebo comparator | Drug: Placebo8 hours infusion with saline (NaCl 0.9%) |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Women
- All pre-menopausal women aged above 18 years
- Diagnosed with endometriosis (ultrasound, MRI or previous laparoscopic and/or diagnostic surgery) according to the #Enzian classification [52]. This means that endometriosis is present in the following compartments:
- Mild to severe chronic pelvic pain (NRS scale >= 6). The 11-point NRS scale ranges from '0' representing no pain to '10' representing the worst pain imaginable.
- Resistant to current recommended lines of analgesics (paracetamol, NSAIDs)
Key exclusion criteria (23 listed)
- Pain score <6 out of 10 (NRS) for chronic pelvic pain
- Endometriosis affecting the bladder and ureter
- Increased intracranial pressure
- Poorly regulated hypertension, >180/100mmHg at rest
- Patients with thyroid disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Esketamine hydrochlorideAlso: ketanestEsketamine dosing regimen is set at 0.1 mg/kg/h as starting dosage. Dosage will be gradually increased based on heart rate, oxygen saturation, blood pressure and side effects (e.g. nausea and dissociative effects) during a period of 8 hours to a maximum of 0.5 mg/kg/h (in steps of 0.1-0.3-0.5 mg/kg/hour). This dosage regimen is similar to that used earlier by Sigtermans et al. [1]. | Drug | Esketamine |
| Placebo8 hour infusion with saline (NaCl 0.9%) | Drug | Placebo |
Primary outcome
Chronic pelvic pain
Time frame: 4 weeks after the 8 hour infusion treatment.
The effect of treatment allocation on the NRS score for chronic pelvic pain. The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
14 secondary outcomes
Dysmenorrhea
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Dyschezia
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Dysuria
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Dyspareunia
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Chronic pelvic pain
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Depressive symptoms
Time frame: Baseline, 4 weeks after infusion treatment
Endometriosis associated Quality of Life
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Quality of life in general
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Quality of life in general
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Productivity costs
Time frame: 12 weeks post-infusion treatment
Medical costs
Time frame: Baseline, 12 weeks post-infusion treatment
Pain coping and cognition
Time frame: Baseline, 12 weeks post-infusion treatment
The effect infusion treatment psychedelic effects
Time frame: On the day of infusion (prior to infusion and during infusion)
Treatment experience
Time frame: Directly after infusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2025.
- Background: PubMed 19604642Sigtermans MJ, van Hilten JJ, Bauer MCR, Arbous SM, Marinus J, Sarton EY, Dahan A. Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1. Pain. 2009 Oct;145(3):304-311. doi: 10.1016/j.pain.2009.06.023. Epub 2009 Jul 14.
- Individual participant dataSharing planned: Undecided. upon request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Esketamine hydrochloride in people with Endometriosis and Chronic Pelvic Pain Syndrome, run by Reinier de Graaf Groep at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mathijs Blikkendaal, MD, PhD (070 340 1222, M.Blikkendaal@rdgg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Chronic pelvic pain (time frame: 4 weeks after the 8 hour infusion treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06161805, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2025.