TENS for Testicular Pain (ICO): A Randomized Controlled Trial

Study Overview
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Brief Summary
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Idiopathic Chronic Orchialgia (i.e., testicular pain) is a challenging condition to treat, with unresolved testicular pain leading to distress, diminished activities of daily living and decreased quality of life. Testicular Pain may be caused by a tumor, hernia, infection, trauma, vein compression, cysts, and/or postoperative or radiating pain, though is often times unknown. Non-pharmacologic, conservative pain reduction interventions include heat, ice, scrotal support, physical therapy, and/or counseling, and should often be used as first line of defense. More aggressive, invasive, and non-conservative medical treatment options include medications, nerve blocks, and/or surgery, each of which may be effective, but may be invasive and/or cause serious side effects. However, there is no standard of care for managing the testicular pain and many men do not respond to current biomedical or nonpharmacologic treatment options. Novel, non-invasive treatment options are needed for ICO to improve distress, daily living activities, and quality of life. Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic intervention for acute and chronic pain. This treatment involves the application of electric current through the skin; it is safe, easy to use, and inexpensive. Despite the impact and distress associated with Testicular Pain, only one known study examined the efficacy of TENS for this condition. A 2018 double-blind, randomized controlled study of people with Testicular Pain reported that TENS improved pain and quality of life significantly more than the control condition (analgesia only). This 2018 study lacked a placebo control condition (i.e., unknown whether pain relief was due to the placebo effect, where knowing an intervention is happening leads to an expectation that pain will decrease, and therefore pain perception decreases independent of the intervention). Thus, the aim of this study is to examine the efficacy of TENS on Testicular Pain using a randomized, placebo-controlled design. The results of this study will be used to inform a larger, federally-funded study. i. Primary Aim: To assess the efficacy of TENS for Testicular Pain ii. Secondary Aim: To assess the feasibility of TENS for Testicular Pain iii. Third Aim: To assess the tolerability of TENS for Testicular Pain iii. To assess associations between dispositional pain catastrophizing on responsiveness to the TENS intervention.

Detailed Description
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The overall aim of this study is to examine the efficacy of TENS on Testicular Pain using a randomized, placebo-controlled design. The results of this study will be used to inform a larger, federally-funded study. The study is a prospective, randomized, double-blinded and placebo-controlled crossover design (each participant completes all 3 study conditions) with randomization to 3 study conditions: 1) Active TENS; 2) Placebo TENS; or 3) No Treatment Control. Subjects will be tested 1x/week for 3 weeks. Each subject will receive the 3 treatments in randomized order. Importantly, the experimenter and subject will be blinded to the treatment condition. A second experimenter will administer the Active or Placebo TENS, or the Control to ensure appropriate blinding (to ensure no bias from knowing which TENS condition is given at each visit). Participants. Thirty men with Testicular Pain (lasting >3 months), aged 18-99yrs will be recruited. Exclusion criteria includes: pain intensity rating ≤ 3/10, contraindications for TENS (pacemaker) or TENS use ≤ 5 years. Participants will provide written informed consent, as approved by the University of Iowa Biomedical Institutional Review Board. TENS Treatment. All subjects will receive each of the 3 TENS treatment conditions while sitting in an upright position. Four adhesive electrodes (2in x 2in) will be placed bilaterally on the: 1) sacrum (for pudendal nerve); and 2) groin (ilioinguinal nerve). Active TENS includes high frequency TENS delivered for 30mins at a frequency of 100 Hz and pulse duration of 100μsec using the EMPI Select TENS unit (calibrated using an oscilloscope prior to study). The intensity will be increased until patients feel a maximally strong but comfortable sensation to ensure an analgesic effect. Placebo TENS parameters will be identical to Active TENS (100 Hz and 100 μsec), but a novel placebo TENS unit, previously tested and validated will be used. The placebo device provides a current for 30sec and ramps off over 15sec to zero output. An indicator light remains on so it appears to the subject that the unit is still producing current. This unit has demonstrated nearly 100% blinding of investigators such that the investigator applying the TENS is unable to distinguish between the active and the placebo unit; approximately  50% of subjects are successfully blinded using this unit. The No Treatment Control includes application of TENS electrodes identical to the other 2 conditions, but the unit remains off. This condition will control for potential effects of repeat testing and any placebo effect. Patient Measures. Pain will be assessed before and after TENS each session to measure any within visit changes in pain from the TENS intervention. Pain change will be measured using the: 1) Short-Form McGill Pain Questionnaire 27 with qualitative (i.e., sharp, distressing) and quantitative pain scales; and 2) 10-point numeric pain intensity rating scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable); These pain measures are valid and reliable. Pain medication intake will also be assessed. Finally, pain-related catastrophizing (i.e., coping) will be measured using the Pain Catastrophizing Scale to determine if any responsiveness to TENS intervention is related to dispositional catastrophizing (i.e., their general catastrophizing levels prior to initiating the TENS study interventions).

Official Title
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TENS for Patients With Chronic Testicular Pain (ICO)

Conditions
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Pain Management

Intervention / Treatment
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* Device: Transcutaneous Electrical Nerve Stimulation (TENS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years to 99; Diagnosis of Idiopathic Chronic Orchialgia (ICO) English Speaking (does not need to be native language) Exclusion Criteria: Pain intensity rating less than 2/10 at time of first session Inability to read or write Inability to follow directions 4 .Contraindications for TENS (Nickel allergy, pacemaker, open wound in TENS application area) 5. TENS use in last 5 years.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The study is a prospective, randomized, double-blinded and placebo-controlled crossover design (all participants complete each of the 3 conditions) with randomization to: 1) Active TENS; 2) Placebo TENS; or 3) No Treatment Control. Each subject will receive the 3 TENS treatments in randomized order (one visit per week in three separate weeks). The visits do not have to take place in three consecutive weeks (will depend on participant scheduling preferences), but all three visits must take place within one year
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Sensation TENS<br>Active TENS is delivered for 30mins at a frequency of 100 Hz and pulse duration of 100μsec using the EMPI Select TENS unit (calibrated using an oscilloscope prior to study). The intensity will be increased until patients feel a maximally strong but comfortable sensation to ensure an analgesic effect. | Device: Transcutaneous Electrical Nerve Stimulation (TENS)<br>* Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic intervention for acute and chronic pain. This treatment involves the application of electric current through the skin; it is safe, easy to use, and inexpensive<br>|
| Placebo Comparator: Low Sensation TENS<br>Placebo TENS parameters will be identical to Active TENS (100 Hz and 100 μsec), but a novel placebo TENS unit, previously tested and validated will be used (Rakel et al., 2010). The placebo device provides a current for 30sec and ramps off over 15sec to zero output. An indicator light remains on so it appears to the subject that the unit is still producing current. This unit has demonstrated nearly 100% blinding of investigators such that the investigator applying the TENS is unable to distinguish between the active and the placebo unit; approximately  50% of subjects are successfully blinded using this unit. | Device: Transcutaneous Electrical Nerve Stimulation (TENS)<br>* Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic intervention for acute and chronic pain. This treatment involves the application of electric current through the skin; it is safe, easy to use, and inexpensive<br>|
| No Intervention: No Treatment Control<br>The No Treatment Control includes application of TENS electrodes identical to the other 2 conditions, but the unit remains off. This condition will control for potential effects of repeat testing and any placebo effect. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Short-Form McGill Pain Questionnaire (MPQ) Pain Scores | Qualitative (e.g.sharp, distressing) and quantitative pain scales. Quantitative pain scale consists of 15 descriptors (11 sensory, 4 affective) which are rated on an intensity scale of 0 = none, 1=mild, 2=moderate, 3=severe. | This outcome measure will be used within 10 minutes of the start of each visit (right before TENS is applied) and 30 minutes after TENS is applied (within visit MPQ change) to assess the within visit change in MPQ pain. | 
| Change in 10-point Numeric Pain Intensity Rating Scale (NRS) pain scores | Quantitative pain scale ranging from 0 (no pain) to 10 (worst pain imaginable) | This outcome measure will be used within 10 minutes of the start of each visit (right before TENS is applied) and 30 minutes after TENS is applied (within visit NRS change) to assess the within visit change in NRS pain. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Catastrophizing Scale (PCS) | Measurement of pain-related coping | This outcome measure will be used at the start of the study (after they consent; baseline). PCS scores range from 0-52 and higher scores mean worse catastrophizing. A decrease in PCS scores is a good outcome. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Testicular, Transcutaneous electric nerve stimulation, Idiopathic chronic orchialgia, Testicular Pain, Chronic Pain, Scrotum