Endometriosis-related PainNCT04179149
Enriched Environments in Endometriosis
A study testing Environmental enrichment in people with Endometriosis-related Pain and Endometriosis, run by Ponce Medical School Foundation, Inc. at 1 site in Puerto Rico.
Trial summary
The investigators propose to conduct a randomized behavioral trial that will produce a clinically useful multi-level integrative medicine model to be used in stress- and inflammation-related disorders that can easily be implemented with current pharmacological interventions to alleviate pain and improve QoL. Read more about this study
- Who is it for?
- Ages 18 to 49 years, women only
- Conditions the study is for
- Endometriosis-related Pain, Endometriosis, Pelvic Pain
- What is being tested?
- Environmental enrichment
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 sitePuerto Rico
- Study dates
- 13 Sep 2019to 31 Jul 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 49 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- premenopausal adult women
- adults 18 and 49 y/o
- diagnosed with endometriosis by surgery
- symptomatic
- refractory to hormonal treatment
- able to provide written informed consent
Who cannot join
- Pregnant women (or who become pregnant during the study period)
- Asymptomatic
- Documented visual, cognitive or physical impairment that would interfere with participation or consent.
- Currently under mental health pharmacological treatment
- Currently using steroid medications.
- Diagnosis of pain syndromes (e.g., fibromyalgia, chronic fatigue syndrome).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Enriched Environments: a Multi-level Integrative Medicine Intervention for Endometriosis
The investigators propose to conduct a randomized behavioral trial that will produce a clinically useful multi-level integrative medicine model to be used in stress- and inflammation-related disorders that can easily be implemented with current pharmacological interventions to alleviate pain and improve QoL.
Read the detailed description
Endometriosis is a chronic inflammatory and painful condition that affects 176 million women in their reproductive years worldwide, and has substantial costs related to health care and loss in work productivity. The symptoms of endometriosis-chronic, incapacitating pain and infertility-cause high levels of stress, leading to poor quality of life (QoL) in affected women. Stress is known to affect the physiology of pelvic organs and to disturb the hypothalamic-pituitary-adrenal (HPA) axis leading to chronic, painful, inflammatory disorders. The team has documented a relationship between stress, HPA dysregulation and endometriosis. In an animal model the team demonstrated that stress exacerbates disease manifestations whereas the ability to control the level of stress results in smaller lesions and less inflammation. Further, the team has identified social support as one of the parameters that most significantly impacts QoL in women with endometriosis. Environmental enrichment (EE) can produce beneficial effects in models of chronic diseases improving anxiety and immune-related disturbances, and can block the effects of chronic stress on brain hippocampal integrity. The team recently found that EE can effectively minimize lesion size and numbers, and also decreased anxiety in this animal model. Together, these data support the basic premise of this proposal: EE interventions can overcome chronic stress thus reversing the negative influences on mental health status (depression/anxiety levels), inflammation/HPA axis (inflammatory cytokines, cortisol), and clinical course (pain levels) of endometriosis, leading to improved QoL. The central objective of this study is to refine and test a multi-modal intervention based on the EE paradigm tested in our animal model and translated it to the human scenario, to produce data on its effectiveness. The team hypothesizes that the EE interventions can be effectively adapted for women with endometriosis resulting in pain reduction and improved QoL. To test our hypothesis, our multidisciplinary team with combined expertise in endometriosis, psychology, physiology, neuroscience, gynecology, and stress management has adapted the experimental EE model to the human scenario. By applying a combined approach (systematic review of the literature, and input from a patient advisory committee) the team has developed six EE modules to be tested in human subjects. This study consists of two specific aims. In aim 1, the team will assess feasibility and acceptability of the EE interventions through a collaborative approach involving a patient population to refine EE modules. Under aim 2, the team will conduct a randomized clinical trial (RCT) of the EE intervention to determine its efficacy in improvement of pelvic pain and QoL (primary outcomes), and inflammation, HPA axis disturbances, and mental health (depression, anxiety) (secondary outcomes), measured before and after the intervention. With this purpose, the team will use a case control study design for the RCT where cases will receive the intervention as an adjuvant to standard gynecologic care for endometriosis, while controls will receive standard of care only. The proposed work will produce a clinically useful multi-level integrative medicine model to be used in stress- and inflammation-related disorders that can easily be implemented with current pharmacological interventions to alleviate pain and improve QoL.
- Conditions
- Endometriosis-related Pain, Endometriosis, Pelvic Pain, Quality of Life, Inflammation Pelvic
- Being tested
- Environmental enrichment
- Keywords
- endometriosis, chronic pelvic pain, quality of life, inflammation, stress
- Medical subject headings
- Endometriosis, Pelvic Pain, Pelvic Inflammatory Disease, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Environmental enrichmentBehavioural
The experimental group will participate in six modules that mimic and integrate the three hallmarks of environmental enrichment: social interaction (more animals per cage = support group meetings, online support), novelty (toys and activities = exposure to new hands-on activities), and larger enclosures (larger cages = meetings in open environments). There will be 2 interventions per month, for three months, and a follow up 3 months after the end of the intervention
| Study group | Role | What they receive |
|---|---|---|
| Environmental enrichment | Experimental | Subjects randomized to the intervention condition will receive the environmental enrichment intervention (social support, open spaces, novel stress relief activities) as an adjuvant to standard gynecological care consisting of hormonal, analgesic or surgical treatment as necessary according to their symptoms during the study period. Receives: Behavioral: Environmental enrichment |
| Controls | No intervention | Participants randomized to the control condition will receive only standard care as necessary according to their symptoms during the study period plus an online patient training module. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain Perception
Mean level of maximum pain using the Visual Analog Scale (VAS), in which 1 is no pain and 10 is the worst pain imaginable. Categories: 1-4 low pain; 5-7 moderate pain; 8-10 severe pain. Therefore, the higher the score in the VAS the higher the pain level.
Measured: at baseline, at end of the intervention and 3 months after the end of intervention
Quality of Life (QoL)
QoL global impact scores measured using the Endometriosis Health Profile 30 (EHP-30), a disease-specific questionnaire to measure health related quality of life. The EHP-30 was developed by Jones et al., in 2001. Part 1 The first part contains 30 questions relevant to all women with endometriosis covering five areas: pain, emotional well-being, control and powerlessness, social support and self imaging scales. Each domain score is calculated by dividing the total scores of each item in the domain by the maximum possible score of all items in the domain multiplied by 100. Our outcome of interest is the global impact score, calculated as the mean of all completed subscale scores, with a range of 0 to 100. The global impact score ranges from 0 (indicating the best health status) to 100 (indicating the worst health status). No subscales are reported.
Measured: at baseline, at end of the intervention and 3 months after the end of intervention (for intervention); at baseline and end of intervention (for controls)
Secondary outcomes (3)
Perceived Stress Levels 14
Perceived stress levels will be measured using the Perceived Stress Scale 14 at baseline, end of interventions and 3 months from the end of intervention for the intervention group, but only at baseline and end of the intervention for the control group. The survey asks the following 14 questions about stressful situations and helps determine what stress is to the participant and how stressful they feel their life to be. Higher scores indicate higher levels of stress.
The 14 items are scored from 0 to 4. Total scores range from 0 to 56. Score categories are:
Low Stress (scores 0 - 18) Moderate Stress (scores 19 - 37) High Stress (scores 38 - 56)
Measured: at baseline, at end of the intervention and 3 months after the end of intervention (for the intervention); at baseline and end of the intervention (for controls)
Depressive Symptomatology
The Patient Health Questionnaire-8 (PHQ-8) is a validated self-report tool used to assess the severity of depressive symptoms over the previous two weeks. The PHQ-8 includes 8 items, each scored on a 4-point scale:
0 = Not at all
- = Several days
- = More than half the days
- = Nearly every day Total score range: 0 to 24 Directionality: Higher scores indicate greater depressive symptom severity (i.e., worse outcomes).
Interpretation of total scores:
0-4: None to minimal depression 5-9: Mild depression 10-14: Moderate depression 15-19: Moderately severe depression 20-24: Severe depression The PHQ-8 was assessed at baseline, immediately post-intervention, and at 3-month follow-up for the intervention group, and at baseline and post-intervention for the control group.
Measured: at baseline, at end of the intervention and 3 months after the end of intervention; and at baseline and post-intervention for the control group.
Anxiety Symptomatology
General Anxiety Disorder 7 (GAD-7) survey assessed at baseline, end of intervention and 3 months from the end of intervention. The GAD-7 scores were also represented with clinical categorizations of anxiety levels as follows: GAD-7 score of 0-4 (none), 5-9 (mild), 10-14 (moderate), and 15-21 (severe).
Measured: at baseline, at end of the intervention and 3 months after the end of intervention (for the intervention group) and at baseline and end of the intervention (for the control group)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2019
- Study start13 Sep 2019
- Primary completion30 Jun 2022
- Study completion31 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Endometriosis-related PainStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In this RCT study, subjects randomized to the intervention condition will receive the Environmental Enrichment (EE) intervention as an adjuvant to standard gynecological care consisting of hormonal, analgesic or surgical treatment as necessary according to their symptoms during the study period. Participants randomized to the control condition will receive only standard care as necessary according to their symptoms during the study period in addition to an online patient training online seminar.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ponce Medical School Foundation, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Oxford, DHR Health Institute for Research and Development
- Responsible party
- Sponsor
- Investigators
- Idhaliz Flores, PhD, Principal investigator, Ponce Medical School Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04179149
- Sponsor's protocol ID
- 1R21HD098481-01
- Status last verified
- May 2025
- First submitted
- 7 Oct 2019
- Last updated
- 23 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: At this point, no individual patient data will be made available to other investigators
Publications
Nieves-Vazquez CI, Detres-Marquez AC, Torres-Reveron A, Appleyard CB, Llorens-De Jesus AP, Resto IN, Lopez-Rodriguez V, Ramos-Echevarria PM, Castro EM, Flores I. Feasibility and acceptability of an adapted environmental enrichment intervention for endometriosis: A pilot study. Front Glob Womens Health. 2023 Jan 4;3:1058559. doi: 10.3389/fgwh.2022.1058559. eCollection 2022.
PubMed 36683601De Hoyos G, Ramos-Sostre D, Torres-Reveron A, Barros-Cartagena B, Lopez-Rodriguez V, Nieves-Vazquez C, Santiago-Saavedra F, Appleyard CB, Castro EM, Flores I. Efficacy of an environmental enrichment intervention for endometriosis: a pilot study. Front Psychol. 2023 Oct 10;14:1225790. doi: 10.3389/fpsyg.2023.1225790. eCollection 2023.
PubMed 37885745
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enriched Environments: a Multi-level Integrative Medicine Intervention for Endometriosis
- ClinicalTrials.gov ID
- NCT04179149
- Acronym / sponsor ID
- 1R21HD098481-01
- Conditions
- Endometriosis-related Pain, Endometriosis, Pelvic Pain, Quality of Life, Inflammation Pelvic
- Keywords
- endometriosis, chronic pelvic pain, quality of life, inflammation, stress
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Ponce Medical School Foundation, Inc.Industry (pharma, biotech, devices)
- Collaborators
- University of Oxford, DHR Health Institute for Research and Development
- Study start
- 13 Sep 2019 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 31 Jul 2022 (actual)
- First posted
- 27 Nov 2019 (actual)
- Results
- Posted 23 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators propose to conduct a randomized behavioral trial that will produce a clinically useful multi-level integrative medicine model to be used in stress- and inflammation-related disorders that can easily be implemented with current pharmacological interventions to alleviate pain and improve QoL.
Detailed description
Endometriosis is a chronic inflammatory and painful condition that affects 176 million women in their reproductive years worldwide, and has substantial costs related to health care and loss in work productivity. The symptoms of endometriosis-chronic, incapacitating pain and infertility-cause high levels of stress, leading to poor quality of life (QoL) in affected women. Stress is known to affect the physiology of pelvic organs and to disturb the hypothalamic-pituitary-adrenal (HPA) axis leading to chronic, painful, inflammatory disorders. The team has documented a relationship between stress, HPA dysregulation and endometriosis. In an animal model the team demonstrated that stress exacerbates disease manifestations whereas the ability to control the level of stress results in smaller lesions and less inflammation. Further, the team has identified social support as one of the parameters that most significantly impacts QoL in women with endometriosis. Environmental enrichment (EE) can produce beneficial effects in models of chronic diseases improving anxiety and immune-related disturbances, and can block the effects of chronic stress on brain hippocampal integrity. The team recently found that EE can effectively minimize lesion size and numbers, and also decreased anxiety in this animal model. Together, these data support the basic premise of this proposal: EE interventions can overcome chronic stress thus reversing the negative influences on mental health status (depression/anxiety levels), inflammation/HPA axis (inflammatory cytokines, cortisol), and clinical course (pain levels) of endometriosis, leading to improved QoL. The central objective of this study is to refine and test a multi-modal intervention based on the EE paradigm tested in our animal model and translated it to the human scenario, to produce data on its effectiveness. The team hypothesizes that the EE interventions can be effectively adapted for women with endometriosis resulting in pain reduction and improved QoL. To test our hypothesis, our multidisciplinary team with combined expertise in endometriosis, psychology, physiology, neuroscience, gynecology, and stress management has adapted the experimental EE model to the human scenario. By applying a combined approach (systematic review of the literature, and input from a patient advisory committee) the team has developed six EE modules to be tested in human subjects. This study consists of two specific aims. In aim 1, the team will assess feasibility and acceptability of the EE interventions through a collaborative approach involving a patient population to refine EE modules. Under aim 2, the team will conduct a randomized clinical trial (RCT) of the EE intervention to determine its efficacy in improvement of pelvic pain and QoL (primary outcomes), and inflammation, HPA axis disturbances, and mental health (depression, anxiety) (secondary outcomes), measured before and after the intervention. With this purpose, the team will use a case control study design for the RCT where cases will receive the intervention as an adjuvant to standard gynecologic care for endometriosis, while controls will receive standard of care only. The proposed work will produce a clinically useful multi-level integrative medicine model to be used in stress- and inflammation-related disorders that can easily be implemented with current pharmacological interventions to alleviate pain and improve QoL.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- In this RCT study, subjects randomized to the intervention condition will receive the Environmental Enrichment (EE) intervention as an adjuvant to standard gynecological care consisting of hormonal, analgesic or surgical treatment as necessary according to their symptoms during the study period. Participants randomized to the control condition will receive only standard care as necessary according to their symptoms during the study period in addition to an online patient training online seminar.
| Arm | Type | Receives |
|---|---|---|
| Environmental enrichment | Experimental | Behavioral: Environmental enrichmentSubjects randomized to the intervention condition will receive the environmental enrichment intervention (social support, open spaces, novel stress relief activities) as an adjuvant to standard gynecological care consisting of hormonal, analgesic or surgical treatment as necessary according to their symptoms during the study period. |
| Controls | No intervention | –Participants randomized to the control condition will receive only standard care as necessary according to their symptoms during the study period plus an online patient training module. |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- premenopausal adult women
- adults 18 and 49 y/o
- diagnosed with endometriosis by surgery
- symptomatic
- refractory to hormonal treatment
Key exclusion criteria (6 listed)
- Pregnant women (or who become pregnant during the study period)
- Asymptomatic
- Documented visual, cognitive or physical impairment that would interfere with participation or consent.
- Currently under mental health pharmacological treatment
- Currently using steroid medications.
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 |
|---|---|---|
| Environmental enrichmentThe experimental group will participate in six modules that mimic and integrate the three hallmarks of environmental enrichment: social interaction (more animals per cage = support group meetings, online support), novelty (toys and activities = exposure to new hands-on activities), and larger enclosures (larger cages = meetings in open environments). There will be 2 interventions per month, for three months, and a follow up 3 months after the end of the intervention | Behavioural | Environmental enrichment |
Primary outcome
Pain Perception
Time frame: at baseline, at end of the intervention and 3 months after the end of intervention
Mean level of maximum pain using the Visual Analog Scale (VAS), in which 1 is no pain and 10 is the worst pain imaginable. Categories: 1-4 low pain; 5-7 moderate pain; 8-10 severe pain. Therefore, the higher the score in the VAS the higher the pain level.
Quality of Life (QoL)
Time frame: at baseline, at end of the intervention and 3 months after the end of intervention (for intervention); at baseline and end of intervention (for controls)
QoL global impact scores measured using the Endometriosis Health Profile 30 (EHP-30), a disease-specific questionnaire to measure health related quality of life. The EHP-30 was developed by Jones et al., in 2001. Part 1 The first part contains 30 questions relevant to all women with endometriosis covering five areas: pain, emotional well-being, control and powerlessness, social support and self imaging scales. Each domain score is calculated by dividing the total scores of each item in the domain by the maximum possible score of all items in the domain multiplied by 100. Our outcome of interest is the global impact score, calculated as the mean of all completed subscale scores, with a range of 0 to 100. The global impact score ranges from 0 (indicating the best health status) to 100 (indicating the worst health status). No subscales are reported.
3 secondary outcomes
Perceived Stress Levels 14
Time frame: at baseline, at end of the intervention and 3 months after the end of intervention (for the intervention); at baseline and end of the intervention (for controls)
Depressive Symptomatology
Time frame: at baseline, at end of the intervention and 3 months after the end of intervention; and at baseline and post-intervention for the control group.
Anxiety Symptomatology
Time frame: at baseline, at end of the intervention and 3 months after the end of intervention (for the intervention group) and at baseline and end of the intervention (for the control group)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 36683601Nieves-Vazquez CI, Detres-Marquez AC, Torres-Reveron A, Appleyard CB, Llorens-De Jesus AP, Resto IN, Lopez-Rodriguez V, Ramos-Echevarria PM, Castro EM, Flores I. Feasibility and acceptability of an adapted environmental enrichment intervention for endometriosis: A pilot study. Front Glob Womens Health. 2023 Jan 4;3:1058559. doi: 10.3389/fgwh.2022.1058559. eCollection 2022.
- Results publication: PubMed 37885745De Hoyos G, Ramos-Sostre D, Torres-Reveron A, Barros-Cartagena B, Lopez-Rodriguez V, Nieves-Vazquez C, Santiago-Saavedra F, Appleyard CB, Castro EM, Flores I. Efficacy of an environmental enrichment intervention for endometriosis: a pilot study. Front Psychol. 2023 Oct 10;14:1225790. doi: 10.3389/fpsyg.2023.1225790. eCollection 2023.
- Individual participant dataSharing planned: No. At this point, no individual patient data will be made available to other investigators
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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. This study is not recruiting at the moment.
Idhaliz Flores, PhD principal investigator
Ponce Medical School Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Environmental enrichment in people with Endometriosis-related Pain and Endometriosis, run by Ponce Medical School Foundation, Inc. at 1 site in Puerto Rico.
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 6 inclusion and 6 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: finished, as of the sponsor's last update on 23 May 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 Puerto Rico. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain Perception (time frame: at baseline, at end of the intervention and 3 months after the end of intervention). The study lists 2 primary outcomes in all. 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 NCT04179149, which also lists 2 linked publications.
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 23 May 2025; AzTrials last refreshed its copy on 29 Oct 2026.