Abdominal Neuromuscular Electrical Stimulation to Treat Neurogenic Bowel Dysfunction in Chronic SCI

Neurogenic Bowel Dysfunction (NBD) is a debilitating complication affecting the majority of individuals with spinal cord injury (SCI), resulting from disrupted autonomic and somatic neural pathways regulating colonic peristalsis and sphincter control. Clinically, NBD manifests as prolonged defecation routines, severe constipation, fecal incontinence, and abdominal distension, with approximately 55% of individuals reporting moderate to severe deterioration in quality of life due to restrictive routines, anxiety over accidental episodes, and caregiver dependency. In severe cases, bowel management requires several hours each day and represents a leading source of secondary morbidity and hospital readmission. In addition, prolonged gastrointestinal transit in SCI alters the gut luminal environment, causing mucosal dysbiosis, depletion of beneficial short-chain fatty acid-producing taxa, and accumulation of potentially deleterious proteolytic fermentation metabolites.

Neuromuscular electrical stimulation (NMES) applied to the abdominal wall musculature is a non-invasive intervention designed to improve bowel function. Historically, abdominal NMES has been applied at suprathreshold intensities to trigger visible tetanic muscle contractions, based on the premise that increased intra-abdominal pressure mechanically facilitates colonic transit and defecation. However, pilot findings and emerging neurophysiological data indicate that sub-motor (sensory) stimulation may independently modulate autonomic enteric pathways via afferent sensory signaling to the spinal cord. In a preliminary single-center pilot trial (NCT04914975, N = 20), daily home-based abdominal NMES applied for 30 minutes prior to scheduled bowel care significantly reduced defecation time and whole-gut transit time. Notably, participants with neurological injury levels below T12 who possessed intact voluntary abdominal motor control also derived clinical benefits, indicating that the underlying mechanisms extend beyond mechanical efferent activation to include sensory afferent neuromodulation.

The ESBo-SCI trial is a randomized, active-controlled, two-period cross-over clinical trial designed to compare the clinical and physiological efficacy of motor-level versus sensory-level abdominal NMES in individuals with chronic SCI. The protocol spans an overall duration of 38 weeks. Following a 2-week standardized baseline phase of prospective documentation without electrical stimulation, participants complete a 12-week intervention period (Stimulation Block I) with either motor NMES or sensory NMES as determined by randomization. This is followed by a 6-week washout phase without electrical stimulation to eliminate potential carry-over effects. Participants then cross over to the alternate stimulation modality for a second 12-week intervention period (Stimulation Block II), concluding with a 6-week follow-up observation phase to determine the durability and persistence of treatment effects. Throughout both 12-week intervention blocks, participants self-administer the stimulation at home for 30 minutes immediately preceding their scheduled bowel routine using certified, current-controlled clinical stimulators. Electrical current intensity is individualized through on-site threshold testing prior to initiating each stimulation block. The motor threshold is defined as the lowest current intensity eliciting a visible muscle twitch within the stimulated area. For the sensory NMES modality, the current amplitude is fixed at 10% below this motor threshold, ensuring activation of cutaneous and subcutaneous sensory afferents without triggering visible muscle contraction. For the motor NMES modality, current amplitude is adjusted above the motor threshold to evoke visible, robust, tetanic abdominal muscle contractions that remain comfortable and tolerable to the participant.

Participants are randomized in a 1:1 allocation to determine the sequence of interventions (motor NMES first versus sensory NMES first).

Laboratory personnel and statisticians remain blinded to treatment sequence and stimulation modality. Participants are masked to the primary study hypotheses and sequence allocation, remaining uninformed regarding which stimulation mode is hypothesized to be superior. The primary hypothesis posits that motor NMES produces a significantly greater reduction in defecation time than sensory NMES, mediated primarily by mechanical intra-abdominal pressure generation combined with efferent motor contractions. The mechanistic hypothesis posits that if sensory NMES yields equivalent or superior clinical improvements, therapeutic benefits will be attributed primarily to afferent somatosensory neuromodulation acting on autonomic spinal and enteric circuits.

A total target enrollment of 41 participants is planned to account for anticipated attrition and provide 33 evaluable participants, ensuring statistical power to detect a clinically meaningful difference in defecation time. Differences between stimulation modalities and study phases will be analyzed using repeated-measures linear mixed-effects models with a random intercept for individual participants, treating the first week of each intervention block as an accommodation run-in phase. All prospective participant logs and clinical questionnaires are managed through an encrypted, web-based electronic data capture system using dedicated tablet computers.

Stimulation is delivered via two independent channels using four self-adhesive surface electrodes placed bilaterally across the abdominal wall over the rectus abdominis and external oblique muscles. Stimulation is administered with a symmetrical rectangular biphasic current, 40 Hz, 300 µs.

Threshold testing is performed at on-site visits prior to initiating each stimulation block:

Motor Threshold Definition: The lowest electrical current intensity eliciting a visible muscle twitch within the stimulated abdominal area.

In this modality, the sensity modality, the current amplitude is fixed at 10% below the individually determined motor threshold, ensuring activation of cutaneous and subcutaneous sensory afferents without triggering visible muscle contraction.

Participants will stimulate with their individually determined amplitude.

Other: Motor NMES Modality

Stimulation is delivered via two independent channels using four self-adhesive surface electrodes (5 cm × 9 cm; Axelgaard PALS) placed bilaterally across the abdominal wall over the rectus abdominis and external oblique muscles.

Current Type: Symmetrical rectangular biphasic current. Frequency: 40 Hz. Pulse Duration: 300 microseconds (µs). Duty Cycle: 8 seconds ON (incorporating 2 seconds ramp-up and 2 seconds ramp-down) followed by 3 seconds OFF.

In this modality, the motor NMES modality, the current amplitude is adjusted above motor threshold to evoke a visible, robust, tetanic abdominal muscle contraction that remains comfortable and tolerable to the participant.

Participants will stimulate with their individually determined amplitude, that is above the sensory threshold.

Other: Sensory NMES Modality

Stimulation is delivered via two independent channels using four self-adhesive surface electrodes (5 cm × 9 cm; Axelgaard PALS) placed bilaterally across the abdominal wall over the rectus abdominis and external oblique muscles.

• Current Type: Symmetrical rectangular biphasic current.
• Frequency: 40 Hz.
• Pulse Duration: 300 µs.

Threshold testing is performed at on-site visits prior to initiating each stimulation block:

• Motor Threshold Definition: The lowest electrical current intensity eliciting a visible muscle twitch within the stimulated abdominal area.
• Sensory NMES Modality: Current amplitude is fixed at 10% below the individually determined motor threshold, ensuring activation of cutaneous and subcutaneous sensory afferents without triggering visible muscle contraction.

Stimulation is delivered via two independent channels using four self-adhesive surface electrodes (5 cm × 9 cm; Axelgaard PALS) placed bilaterally across the abdominal wall over the rectus abdominis and external oblique muscles.

• Current Type: Symmetrical rectangular biphasic current.
• Frequency: 40 Hz.
• Pulse Duration: 300 microseconds (µs).
• Duty Cycle: 8 seconds ON (incorporating 2 seconds ramp-up and 2 seconds ramp-down) followed by 3 seconds OFF.

Motor NMES Modality: Current amplitude is adjusted above motor threshold to evoke a visible, robust, tetanic abdominal muscle contraction that remains comfortable and tolerable to the participant.

Plazo: Defecation time will be assessed with a stool diary over the entire study period of 38 week depending on the bowel movements per week.

Defined as the elapsed duration from the expulsion of the first stool until the expulsion of the last stool. Participants prospectively record precise timestamps for each bowel routine in a daily electronic diary. The primary endpoint is the intra-individual change in mean weekly defecation time between baseline and the two stimulation modalities (excluding the first week of each stimulation block as a run-in phase).

Plazo: Defecation will be assessed in form of a diary over the entire study period of 38 weeks depending on the number of defecation sessions per week

Defined as the elapsed duration from the expulsion of the first stool until the expulsion of the last stool. Participants prospectively record precise timestamps for each bowel routine in a daily electronic diary. The primary endpoint is the intra-individual change in mean weekly defecation time between baseline and the two stimulation modalities (excluding the first week of each stimulation block as a run-in phase).

Plazo: The Blue Dye Test will performed 5 times over the entire study period of 38 weeks.

Evaluated using a validated home test administered prior to study visits:

Standardized Blue Dye Test: Following an overnight fast (≥8 hours), participants ingest two plain rice crackers and swallow a single 0.68 mL gelatin capsule containing 0.25 g food-grade blue dye powder (\~60 mg combined E131/E132; Hollinger Farbpulver Blau) with \~100 mL water. Diet, activity, and bowel medications remain unchanged, with intensely colored foods avoided for 48 hours. WGTT is defined as the duration between capsule ingestion and the first appearance of blue or blue-green stool.

Plazo: The Corn Test will performed 5 times over the entire study period of 38 weeks.

Evaluated using a validated home test administered prior to study visits:

Corn Test: Ingestion of 140 g of canned sweetcorn; elapsed time to the first visual identification of excreted corn kernels is recorded.

Plazo: The BSFS is included in the stool diary and will be filled in at the every defecation time point over the entire study period of 38 weeks.

Bristol Stool Form Scale (BSFS; range: Type 1 \[separate hard lumps\] to Type 7 \[entirely liquid\]), logged per defecation event

Plazo: The NBD score will be assessed 5 times over the entire study period of 38 weeks.

Validated 10-item clinical questionnaire assessing fecal incontinence, constipation, defecation duration, medication dependence, and lifestyle restriction (total score 0 to 47; higher scores indicate greater severity).

Plazo: The GIQLI will be assessed 5 times over the entire study period of 38 weeks.

Total Score Range: 0 to 144 points (derived from 36 items, each rated on a 5-point Likert scale from 0 to 4).

Higher scores indicate a better quality of life, meaning fewer symptoms and better daily functioning.

Disease-specific health-related quality of life instrument evaluating gastrointestinal symptoms, physical functioning, emotional state, social performance, and medical treatment burden.

Plazo: The Gut Microbiome Profiling consisting of stool probes will be assessed 5 times over the entire study period of 38 weeks.

Fecal samples are collected at scheduled visits using ambient-temperature DNA stabilization kits (DNA Genotek) or home frozen at -20°C prior to transport on cold packs and storage at -80°C. Stool aliquots undergo enzymatic pre-lysis and bead-beating prior to silica-membrane DNA purification. Full-length 16S rRNA genes (V1-V9 regions, \~1.5 kb) are amplified (primers 27F/1492R) and sequenced on Oxford Nanopore MinION platforms. Sequences are demultiplexed, filtered (Q ≥ 10; 1,400-1,650 bp), and taxonomically classified against the SILVA 138 database to quantify alpha/beta diversity and relative abundance of short-chain fatty acid-producing versus inflammation-associated taxa.

Plazo: The diary will be filled in electronically on daily base over the entire study period of 38 weeks.

Daily tracking includes time of routine initiation, first stool expulsion, last stool expulsion as the absolute defecation time.

Plazo: The diary will be filled in electronically on daily base over the entire study period of 38 weeks.

Daily tracking includes time of clean-up start and completion to calculate the relative defecation time.

Plazo: The diary will be filled in electronically on daily base over the entire study period of 38 weeks.

Daily tracking includes time of individual defecation interventions

Plazo: The stimulation parameter will be filled in electronically during the two stimulation periods of 12 weeks each.

The diary includes the stimulation parameter in terms of intensity (amplitude mA)

Plazo: The stimulation parameter will be filled in electronically during the two stimulation periods of 12 weeks each.

The diary includes the stimulation time (minutes)

Plazo: The stimulation parameter will be filled in electronically during the two stimulation periods of 12 weeks each.

The diary includes participants' posture during stimulation

Plazo: The Nutritional Confounders will be assessed twice at baseline (day 1) and at study completion (day 1-3, week 38).

Dietary intake is assessed by using the Cambridge Food Frequency Questionnaire (FFQ).

Plazo: This Lifestyle Confounder will be assessed twice at baseline (day 1) and at study completion (day 1-3, week 38).

Frequency of weekly physical activity will be documented

Plazo: This Lifestyle Confounder will be assessed twice at baseline (day 1) and at study completion (day 1-3, week 38).

Duration of weekly physical activity will be documented

Plazo: This Lifestyle Confounder will be assessed twice at baseline (day 1) and at study completion (day 1-3, week 38).

Type of weekly physical activity will be documented

ESBo-SCI: Abdominal Neuromuscular Electrical Stimulation to Treat Neurogenic Bowel Dysfunction in Chronic SCI