Transcutaneous Electrical Nerve Stimulation for Endometriosis-related Chronic Pain

Study Overview
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Brief Summary
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The study evaluates the effect of TENS (transcutaneous electrical nerve stimulation) as add-on treatment compared with conventional analgesic treatment in patients with endometriosis-related chronic pain. Patients with frequent pain and high pain intensity will be randomized to additional treatment with TENS or conventional treatment for 8 weeks to evaluate the acute effects of TENS treatment (n=40). Patients with endometriosis-related pain that is not frequent or without high pain intensity constitute an external control group. All patients in the study will receive TENS treatment for a total of 16 weeks, for evaluation of long-term effects of TENS treatment.

Detailed Description
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Endometriosis affects approximately one in ten women of childbearing age and may involve both acute pain related to the menstrual cycle and chronic pain. Usual analgesic therapy is often inadequate and/or involves unacceptable side effects and risks with long-term use. Transcutaneous electrical nerve stimulation (TENS) is a patient controlled treatment for pain relief with few side-effects. To date there is limited knowledge of how TENS treatment should be carried out for optimal pain relief in this patient group. The aim of the study is asses the effect of TENS as add-on treatment compared with conventional analgesic treatment in patients with endometriosis-related chronic pain. Patients with frequent pain and high pain intensity (≥ 4 according to Numeric Rating Scale, NRS) will be randomized to additional treatment with TENS or conventional treatment for 8 weeks in order to evaluate the acute effects of TENS treatment (n=40). Patients with endometriosis-related pain that is not frequent or without high pain intensity constitute an external control group. All patients in the study will receive TENS treatment for a total of 16 weeks, for evaluation of long-term effects of TENS treatment in chronic endometriosis-related pain. Prior to start of TENS treatment, all patients receive education on chronic endometriosis-related pain and TENS treatment. Study participants will be asked to participate in a qualitative follow-up within the study including a semi-structured individual interview (n=10-15) before intervention and a semi-structured focus group (n=9-15) interview after completion of TENS treatment.

Official Title
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High Frequency, High Intensity Transcutaneous Electrical Nerve Stimulation for Endometriosis-related Chronic Pain - a Randomized Controlled Trial

Conditions
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Endometriosis-related Pain

Intervention / Treatment
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* Device: Transcutaneous electrical nerve stimulation (TENS)
* Other: Conventional analgesic treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Consents to participation in the study Verified endometriosis (by laparoscopy or ultrasound). Chronic endometriosis-related pain (> 3 months), available for TENS treatment Functioning, stable endometriosis-specific hormonal drug therapy. The endometriosis-specific drug therapy must be unchanged for the last 3 months and no gynecological surgical procedures for the treatment of endometriosis are planned during the next 7 months (during study participation). The endometriosis-specific drug therapy does not refer to analgesic therapy for symptom relief of endometriosis-related pain. Exclusion Criteria: Patient with inability to understand and use written and spoken Swedish Patient with pacemaker and/or ICD or other electronic implants Patient with impaired sensation over the painful area Malignant disease with an expected survival <12 months Alcohol or substance abuse Serious untreated psychiatric illness and/or psychological condition that is the primary determinant of the patient's condition Participating in another intervention study with possible impact on current study outcome measures Patient who is using >90 morphine equivalents/day Patient who is electro-acupuncture Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients with frequent pain and high pain intensity (≥ 4 according to Numeric Rating Scale, NRS) will be randomized to additional treatment with TENS or conventional analgesic treatment for 8 weeks in order to evaluate the acute effects of TENS treatment (n=40). Patients with endometriosis-related pain that is not frequent or without high pain intensity constitute an external control group. All patients in the study will receive TENS treatment for a total of 16 weeks, for evaluation of long-term effects of TENS treatment in chronic endometriosis-related pain.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: TENS (transcutaneous electrical nerve stimulation)<br>Patients with endometriosis-related chronic frequent pain and high pain intensity (≥ 4 according to Numeric Rating Scale, NRS) randomized to transcutaneous electrical nerve stimulation as add-on treatment in addition to conventional analgesic treatment. Treatment with transcutaneous electrical nerve stimulation (TENS) during 16 weeks. | Device: Transcutaneous electrical nerve stimulation (TENS)<br>* Treatment with transcutaneous electrical nerve stimulation (TENS) during 16 weeks.<br>|
| Active Comparator: Conventional analgesic treatment<br>Patients with endometriosis related chronic frequent pain and high pain intensity (≥ 4 according to Numeric Rating Scale, NRS) randomized to conventional analgesic treatment for 8 weeks. After 8 weeks the patients are treated with transcutaneous electrical nerve stimulation (TENS) during 16 weeks. | Other: Conventional analgesic treatment<br>* Conventional analgesic treatment. Conventional analgesic treatment may include no pharmacological treatment if the patient does not use any analgesics.<br>|
| Active Comparator: External control group<br>Patients with endometriosis-related pain that is not frequent or without high pain intensity (< 4 according to Numeric Rating Scale, NRS) constitute an external control group. The patients are treated with transcutaneous electrical nerve stimulation as add-on treatment in addition to conventional analgesic treatment. Treatment with transcutaneous electrical nerve stimulation (TENS) during 16 weeks. | Device: Transcutaneous electrical nerve stimulation (TENS)<br>* Treatment with transcutaneous electrical nerve stimulation (TENS) during 16 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity | Pain intensity according to numeric rating scale (score from 0 to 10, where 0 is described as no pain and 10 as worst pain imaginable) with regard to endometriosis-related chronic pain | 8 weeks after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity | Pain intensity according to numeric rating scale (score from 0 to 10, where 0 is described as no pain and 10 as worst pain imaginable) with regard to endometriosis-related chronic pain | 16 weeks after start of TENS treatment | 
| Physical activity | Minutes of physical activity per week at moderate and vigorous intensity physical activity (MVPA), minutes of sedentary behaviour (SED) assessed by accelerometry | 16 weeks after start of TENS treatment | 
| Self-assessed physical activity | Minutes of physical activity per week (physical exercise and daily exercise) and minutes of sedentary behaviour per week. | 16 weeks after start of TENS treatment | 
| Consumption of analgetics | Consumption of primary and secondary analgetics including opioid consumption in morphine equivalent doses | 8 weeks after randomization | 
| Consumption of analgetics | Consumption of primary and secondary analgetics including opioid consumption in morphine equivalent doses | 16 weeks after start of TENS treatment | 
| Change in pain intensity | Pain intensity according to numeric rating scale (score from 0 to 10, where 0 is described as no pain and 10 as worst pain imaginable) with regard to endometriosis-related chronic pain, Likert scale (1= worse, 2= unchanged, 3= slightly improved, 4= much improved, 5 = very much improved,and 6= completely improved). | 8 weeks after randomization | 
| Change in pain intensity | Pain intensity according to numeric rating scale (score from 0 to 10, where 0 is described as no pain and 10 as worst pain imaginable) with regard to endometriosis-related chronic pain, Likert scale (1= worse, 2= unchanged, 3= slightly improved, 4= much improved, 5 = very much improved,and 6= completely improved). | 16 weeks after start of TENS treatment | 
| Health Related Quality of Life (HRQL) according to SF36 | Assessed with RAND Short Form 36 (SF36). The 36 items in the questionnaire are grouped into eight subscale scores: physical functioning, role limitations caused by physical problems, bodily pain, general health, energy/vitality, social functioning, role limitations caused by emotional problems and mental health. The subscale scores range from 0-100, the higher score, the better health related quality of life. | 8 weeks after randomization | 
| Health Related Quality of Life (HRQL) according to SF36 | Assessed with RAND Short Form 36 (SF36). The 36 items in the questionnaire are grouped into eight subscale scores: physical functioning, role limitations caused by physical problems, bodily pain, general health, energy/vitality, social functioning, role limitations caused by emotional problems and mental health. The subscale scores range from 0-100, the higher score, the better health related quality of life. | 16 weeks after start of TENS treatment | 
| Health Related Quality of Life (HRQL) assessed with EQ-5D | Assessed with EQ-5D-5L. The questionnaire comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement. | 8 weeks after randomization | 
| Health Related Quality of Life (HRQL) assessed with EQ-5D | Assessed with EQ-5D-5L. The questionnaire comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement. | 16 weeks after start of TENS treatment | 
| Health Related Quality of Life (HRQL) assessed with EHP 30 | Assessed with Endometriosis Health Profile 30. The EHP score indicate the extent of self-reported ill health on each of the 5 domains measured (Pain, Control and powerlessness, Social support, Emotional well-being, Self-image). Each scale is standardised on a scale of 0 - 100, where 0 indicates the best health status through to 100 worst health status. | 8 weeks after randomization | 
| Health Related Quality of Life (HRQL) assessed with EHP 30 | Assessed with Endometriosis Health Profile 30. The EHP score indicate the extent of self-reported ill health on each of the 5 domains measured (Pain, Control and powerlessness, Social support, Emotional well-being, Self-image). Each scale is standardised on a scale of 0 - 100, where 0 indicates the best health status through to 100 worst health status. | 16 weeks after start of TENS treatment | 
| General Self-Efficacy Scale | The General Self-Efficacy Scale is a 10-item psychometric scale that is designed to assess optimistic self-beliefs to cope with a variety of difficult demands in life, Likert scale (1= Not at all true 2= Hardly true 3= Moderately true 4= Exactly true) | 8 weeks after randomization | 
| General Self-Efficacy Scale | The General Self-Efficacy Scale is a 10-item psychometric scale that is designed to assess optimistic self-beliefs to cope with a variety of difficult demands in life, Likert scale (1= Not at all true 2= Hardly true 3= Moderately true 4= Exactly true) | 16 weeks after start of TENS treatment | 
| Insomnia Severity | Total score from the 7-item Insomnia Severity Index where total score ranges from 0-28 and higher scores indicate greater severity of insomnia. | 8 weeks after randomization | 
| Insomnia Severity | Total score from the 7-item Insomnia Severity Index where total score ranges from 0-28 and higher scores indicate greater severity of insomnia. | 16 weeks after start of TENS treatment | 
| Days of sick-leave | Number of days of sick-leave | 8 weeks after randomization | 
| Days of sick-leave | Number of days of sick-leave | 16 weeks after start of TENS treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endometriosis, Chronic pain, Transcutaneous electrical nerve stimulation