Interrogating the Pathophysiological Mechanisms of Constipation in Patients With Systemic Sclerosis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether transcutaneous electrical acustimulation (TEA) alters systemic sclerosis (SSc)-related colonic and anorectal physiology by enhancing autonomic nervous system (ANS) function. The study will examine the effects of TEA on slow colonic transit (SCT) and rectal hyposensitivity (RH), to examine whether TEA improves autonomic dysfunction and modulates inflammatory pathways.

Official Title
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Interrogating the Pathophysiological Mechanisms of Constipation in Patients With Systemic Sclerosis

Conditions
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Systemic Sclerosis, Constipation, Gastrointestinal Motility Disorder, Autonomic Dysfunction

Intervention / Treatment
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* Device: Transcutaneous Electrical Acustimulation (TEA)
* Device: Sham-TEA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients with SSc-constipation from Aim 1 of the study Patients with SCT (>20% radiopaque marks left in the colon 5 days (120 hours) after swallowing the Sitzmark capsule or patients with RH (defined in Aim 1) Patients not yet on therapy for constipation or patients who continue to experience constipation while on stable therapy for one month prior to TEA. Exclusion Criteria -Patients with symptoms of both diarrhea and constipation but not predominantly symptoms of constipation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcutaneous Electrical Acustimulation (TEA)<br> | Device: Transcutaneous Electrical Acustimulation (TEA)<br>* TEA will then be administrated for 1 hour twice daily for a period of 4 weeks<br>|
| Sham Comparator: Sham-TEA<br> | Device: Sham-TEA<br>* Sham TEA will then be administrated for 1 hour twice daily for a period of 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in slow colonic transit (SCT) | slow colonic transit (SCT) is defined by more than 5 (20%) of Sitz markers retained 5 days after ingestion | baseline, week 4 (visit 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in rectal hyposensitivity as assessed by the anorectal manometry |  | baseline, week 4 (visit 2) | 
| Change in autonomic dysfunction as assessed by the Heart rate variability (HRV) measures |  | baseline, week 4 (visit 2) | 
| Change in autonomic dysfunction as assessed by the COMPASS-31 measures | This is a 31 item questionnaire and scores range from 0-100 a higher score indicating more severe autonomic dysfunction | baseline, week 4 (visit 2) | 
| Change in inflammatory cytokines (IL-6, Tumour Necrosis Factor alpha (TNF-alpha) ), |  | baseline, week 4 (visit 2) |