Afferent Stimulation to Evoke Recto-colonic Reflex for Colonic Motility
Phase: NA
Conditions: Neurogenic Bowel Dysfunction
Sponsor: VA Office of Research and Development

 
 
 
 
 
 
 
 
 
Electrical stimulation to evoke recto-colonic reflex for colonic motility  
Funding Agency: VA RR&D 
Principal Investigator: Steven Brose, DO 
1593201-8/12-3-21/2021  
 

 
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Abstract 
 
This study hopes to characterize the effects of minimally invasive electrical rectal 
stimulation on colonic motility in persons with neurogenic bowel dysfunction. Subjects will 
act as their own controls, with control data being obtained during subjects’ typical bowel 
routines. Outcome measures include bowel emptying duration and amount of stool 
removed. These data will be compared to determine the efficacy of electrical stimulation to 
promote bowel emptying compared to patients’ typical bowel routines, and to provide an 
effect size on the outcome measures of colonic motility for powering future studies. 
We hypothesize that electrical rectal stimulation will produce increased colonic motility 
that results in defecation and that defecation time will be similar to subjects’ typical bowel 
routines. The time required for defecation in response to their typical bowel routine and to 
minimally invasive electrical rectal stimulation will be monitored. Subjects will also be 
asked to report on sensations and comment on electrical stimulation. 
 
 

 
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List of Abbreviations 
LSCDVAMC: Louis Stokes Cleveland DVA Medical Center 
SVAMC: Syracuse VA Medical Center  
SCI: spinal cord injury 
EMG: electromyogram 
AD: autonomic dysreflexia 
NBD: neurogenic bowel dysfunction 
FES: functional electrical stimulation 
IRB: Institutional Review Board 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Contents 
 
1.0 
Study Personnel ........................................................................................................ 5 
2.0 
Introduction .............................................................................................................. 5 
3.0 
Objectives .................................................................................................................. 6 
4.0 
Resources and Personnel .......................................................................................... 6 
5.0 
Study Procedures ...................................................................................................... 7 
5.1 Study Design ............................................................................................................... 7 
5.2 Recruitment Methods ................................................................................................ 8 
5.3 Informed Consent Procedures ................................................................................... 9 
5.4 Inclusion/Exclusion Criteria ..................................................................................... 9 
5.5 Study Evaluations .................................................................................................... 10 
5.6 Data Analysis ............................................................................................................ 10 
5.7 Withdrawal of Subjects ............................................................................................. 11 
6.0 
Reporting .................................................................................................................. 11 
7.0 
Privacy and Confidentiality ...................................................................................... 11 
8.0 
References ............................................................................................................... 12 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Protocol Title: Electrical stimulation to evoke recto-colonic reflex for colonic motility 
 
1.0 Study Personnel 
 
PI: Steven Brose, DO, Chief of the SVAMC SCI Unit  
Co-Investigators: Dennis Bourbeau, PhD, Investigator and Biomedical Engineer at 
Cleveland FES center and LSCDVAMC.       
2.0 Introduction 
 
Loss of bowel function is a major concern for veterans with central nervous disorders, 
such as spinal cord injury (SCI). Over 42,000 veterans have SCI, representing more 
than 15% of the total American population with SCI. Following SCI, the colon is often 
unable to evacuate stools via peristaltic propulsion. Losing bowel function can cause 
constipation, gastro-intestinal complications, and fecal incontinence, severely impacting 
health and quality of life. 
 
The standard of care for individuals with neurogenic bowel dysfunction involves the 
design of a bowel program for predictable and effective elimination of the bowels. A 
bowel program includes diet, fluid intake, activity, and pharmaceutical or mechanical 
rectal stimulation. Approximately 80% of individuals with neurogenic bowel 
dysfunction use digital stimulation of the rectum to reflexively activate the colon, 
improve colonic motility, and facilitate bowel evacuation. However, the bowel routine 
can require over an hour to evacuate the bowels and this process often requires the 
assistance of a caregiver, which adds to the cost of care and reduces independence. 
Restoring bowel function is considered a high priority by individuals with paraplegia, 
but it remains a critically unmet need requiring further development. The top priority 
for individuals with tetraplegia is reaching and hand function, but pelvic functions are 
still of high concern. 
 
Digital rectal distension is the clinical standard for eliciting colon motility. The majority 
of individuals with neurogenic bowel dysfunction use digital rectal stimulation to 
mechanically distend the rectum and reflexively activate colon peristalsis, which loads 
stool into the rectum for bowel emptying. Digital rectal distension takes advantage of an 
existing reflex pathway affecting bowel function. The recto-colonic reflex has been well-
studied in cats, dogs, and humans. Rectal distension activates mechanoreceptors 
innervating the rectum, which sends afferent information via small Aδ and C fibers to 
the sacral spinal cord. This input modulates a spinal reflex pathway that activates motor 
efferent drive to the colon, causing coordinated peristalsis and increasing colonic 
motility. Digital rectal stimulation is effective, but it requires an individual, or a 
caregiver, to reach into the individual’s rectum with gloved fingers. Even with digital 

 
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rectal stimulation and other bowel program tools, the bowel routine still typically 
requires an hour or two to complete. Reliance on digital rectal stimulation is associated 
with lost independence, lost time, lost dignity, and increased caregiver costs. 
Substituting rectal distension for a method that does not include these drawbacks would 
provide positive social and psychological benefits. 
 
We are currently developing approaches using electrical stimulation to improve colonic 
motility as an alternative to digital rectal stimulation and to take advantage of the recto-
colic reflex. Recent preclinical experiments have provided supporting evidence that 
electrical stimulation of the rectum or distal colon can modulate this excitatory recto-
colic reflex and potentially promote bowel emptying. We hope to quantify the effects of 
minimally invasive electrical rectal stimulation, in comparison to subjects’ typical bowel 
emptying routine, on colonic activity in persons with neurogenic bowel dysfunction. 
 
3.0 Objectives 
 
This pilot study hopes to characterize the effects of minimally invasive electrical rectal 
stimulation on colonic motility in persons with neurogenic bowel dysfunction, as well as 
collect data to determine an effect size and so power future studies that measure colonic 
motility in response to electrical stimulation  
Our hypothesis is that electrical rectal stimulation will produce increased colonic 
motility that results in defecation and that defecation time will be similar to subjects’ 
typical bowel routines.  
4.0 Resources and Personnel 
 
All study actives will occur at the SVAMC, in the SCI inpatient clinic.  
Recruitment of subjects will be done by the PI, who will identify potentially eligible 
participants receiving SCI treatment at the SVAMC. Once potential subjects are 
identified, informed consent will be obtained by a research assistant or nurse. Only a 
nurse approved on the study will be responsible for collecting data. 
 
 
 
 
 

 
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5.0 Study Procedures 
 
5.1 Study Design 
 
Experiments will be conducted in the SCI inpatient clinic in 10 individuals with 
neurogenic bowel dysfunction who have stable bowel routines. We will work with 
nursing staff on the study to maintain a consistent bowel emptying schedule for the 
subjects. We will not disrupt the patient’s typical bowel emptying routine. Only the 
Research Nurse will be completing any research related procedures.  Data will be 
collected from subjects over 6 weeks during their typical bowel routines. Then we will 
test minimally invasive electrical rectal stimulation via a rectal probe in a second 6-week 
period. Subjects will be instrumented with a rectal probe and stimulator inserted by the 
Research Nurse only for the duration of those bowel routines and effects are not 
expected to continue past the end of the experiment period. Subjects will return to their 
typical bowel routine at the end of the 6-week stimulation testing period. For patients 
>6 months post-SCI, the control period for the study will consist of their typical digital 
stim bowel routine. Nurses will log dig stim data as they usually do and this data will be 
used as control data for the study. During the experimental phase of the experiment, dig 
stim will be replaced with electrical stimulation. Use of electrical stim will not change 
the patients’ bowel routine otherwise. There is no set schedule for the intervention 
because we are adapting to each patients’ normal bowel routine. The only structure is 
that we have a defined control period using their normal routine, followed by a defined 
experimental period with the electrical stimulation. For a normal bowel routine, 
patients typically receive bowel intervention every other day in a typical week.  
 
For subjects within 6 months of SCI diagnosis, but after the acute spinal shock phase, 
we will instead alternate between periods of control intervention (dig stim) and 
electrical stimulation. This will be done 3-7 times a week to optimize data acquisition, 
rather than having a defined control period followed by a defined experimental period. 
Neither the altered procedure nor the inclusion of patients who are <6 months post-SCI 
will affect the risk level of the study. Acute spinal shock is defined as the period 
immediately following an acute spinal cord injury. This phase resolves 72 hours post-
injury and it is exceptionally rare that a patient in this phase of injury would be in the 
SCI, rather than the ICU.  
 
 
Typical Bowel Routine 
Typical bowel routines usually involve digital rectal stimulation conducted by the 
subject, their nurse, or their caregiver. An individual inserts a gloved finger through the 
anus into the rectum and mechanically distends the rectum by moving back and forth 
against the inside of the rectal wall for approximately 30 seconds. Time is allowed for 
the colon to move and evacuate some stools, then the process is repeated (typically 15-
20 minutes later). Digital rectal stimulation is thus repeated until the colon contents are 
empty, usually marked by the appearance of mucus and no evidence of stools in the 
distal colon or rectum. Some subjects may also receive a mini-enema or other 

 
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suppository to aid in bowel emptying. Individual bowel routine schedules vary but are 
typically conducted 3-5 times a week. 
 
Electrical Rectal Stimulation 
A clinically standard rectal probe electrode will be inserted into the rectum to 
administer electrical stimulation. The probe electrode will only be in place to administer 
bouts of stimulation just as gloved fingers administer digital rectal distension, after 
which it will be removed to allow for bowel emptying. The probe electrode will be 
connected to a Digitimer stimulator DS7A, which is FDA-approved for electrical 
stimulation in human subjects and has been used in our previous, similar experiments 
for bladder function. Stimulation will either be 20 Hz constant frequency or burst 
pattern stimulation delivered as 5-50 pulses at 100-200 Hz once per second. We will 
first determine the stimulation amplitudes at which the subject can sense stimulation 
and at what limit they tolerate stimulation but do not wish to go higher for concern of 
discomfort. We will then apply stimulation within this range, not expected to exceed 40 
mA, which is the typical range we see in similar applications of surface electrical 
stimulation. Stimulation will be administered continuously for the duration of the bowel 
routine. If stimulation does not increase colonic motility and promote defecation, as 
determined by each subject’s baseline data on bowel emptying time, nurse experience, 
or clinician expertise, then we will cease stimulation for that day and return to the 
subject’s typical bowel routine. If stimulation fails to increase colonic motility for bowel 
emptying on 3 or more occasions in a given subject, then we will stop the 6-week 
stimulation period and return that subject to their typical bowel routine. 
 
The procedures in this study involve certain risks, which are similar to the risks of 
digital rectal stimulation, which is part of a participant’s bowel routine. The incremental 
risks involved in performance of these studies are not significantly greater than those 
encountered during a standard bowel routine. However, these risks are outlined in the 
participant’s consent form, along with explanations of what would be done to reduce the 
likelihood of adverse avents, and what would be done should any occur.  
 
 
5.2 Recruitment Methods 
Patients of the SCI unit will be recruited by word of mouth by Dr. Brose at the SVAMC. 
As many patients will be recruited as needed to enroll 10 subjects into the study. 
Eligibility will be assessed via chart review and patient interview by the PI. Those 
expressing interest will be referred to study staff who will explain the study, highlight 
that it is voluntary, and answer any questions.   
Every effort will be made to recruit individuals that are representative of the US 
population. The units treating patients with spinal cord injuries, stroke, or multiple 
sclerosis at the SVAMC have a particularly high proportion of subjects from 
underrepresented minority groups. The majority of individuals with neurogenic bowel 
dysfunction that are available for the study are male. Therefore it is expected that the 
majority of experiments will be performed on men. Every effort will be made to include 
women who should at least represent their prevalence in the spinal cord injured 

 
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population. All candidates will be treated the same with strict adherence to the inclusion 
and exclusion criteria. 
Individuals who do not speak English will not be recruited. However, it is not 
anticipated that non-English speaking potential participants will be encountered. 
Participants will be paid $50 via check sent through the post upon completion or partial 
completion of the study. 
 
5.3 Informed Consent Procedures 
 
Informed consent will be obtained by a member of the research staff, after verbal 
explanation and provision of time for the subject to study the consent form and ask 
questions. The informed consent process will involve meeting with a potential subject in 
a quiet, private area (on the SCI Unit or in a physician's private office), finding out 
whether he or she is capable of giving consent, and discussing the purpose, risks, and 
benefits of participation. We will ensure that all subjects genuinely understand the 
study, that they are aware that participation is entirely voluntary, and that they can 
choose to discontinue participation at any time.  
HIPAA authorization will be discussed with the potential participant at the time the 
patient is interviewed and a copy of the authorization will be given to them for their 
review. Specific information collected will include:  Date of birth, date of spinal injury, 
level of spinal injury, gender, name, medical record number (social security number), 
current medications, previous bladder or urinary tract interventions, current medical 
status, and phone number. This information is being collected because these data are 
used to categorize individuals according to medical condition and allow investigation of 
medically related differences between the responses of different individuals. The 
participant’s social security number will be collected in order to place appropriate 
documentation in the participant’s medical record 
 
5.4 Inclusion/Exclusion Criteria 
 
Inclusion Criteria 
 Neurogenic bowel dysfunction using digital rectal stimulation 
 Neurologically stable 
 Skeletally mature 
 Adults 18 years or greater 
 Multiple Sclerosis or Stroke or Suprasacral SCI 
 Must be past acute spinal shock phase 
Exclusion Criteria 

 
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 Active sepsis 
 Open pressure sores on or around pelvis 
 Significant colon trauma or colostomy 
 History of Autonomic Dysreflexia 
 
5.5 Study Evaluations  
 
Data collection will include standard medical charting and documenting outcome 
measures, such as bowel emptying time as written in section 5.6 Data Analysis. No tests, 
questionnaires, or procedures will be conducted beyond the typical bowel routine or 
stimulation testing described in this protocol. 
 
 
 
 
5.6 Data Analysis 
 
This work is considered a pilot study. Data will be collected to determine an effect size 
and power future studies that measure colonic motility in response to electrical 
stimulation. Therefore, 10 subjects are chosen to provide sufficient data to power a 
future study. 
 
Bowel emptying will be performed by a trained clinician, caregiver, or subject (whoever 
normally performs it for the subject) using standard technique. The bowel routine is 
typically conducted with digital rectal stimulation and/or the insertion of suppositories 
or similar chemical systems. The time that elapses between initial intervention and 
bowel emptying will be measured as bowel emptying time. We will also test electrical 
stimulation to modulate an excitatory recto-colic reflex by stimulating via a rectal probe 
electrode. These systems are clinically available for chronic constipation in other 
indications and are considered minimal risk. We have experience measuring bowel 
activity with these methods. Initial introduction of the rectal probe electrode may cause 
temporary distension of the rectum. To ensure that reflexive activity due to the probe 
does not confound our data, we will wait approximately 5-10 minutes for the colon to 
relax back to baseline activity before beginning the bowel routine with stimulation. 
 
The primary outcome variable is bowel emptying time. Bowel emptying time data are 
not expected to follow a normal distribution. Therefore, the non-parametric Mann-
Whitney rank-sum test with a significance of 0.05 will be used to compare bowel 
emptying times between typical bowel routines and electrical stimulation conditions 

 
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across subjects. We expect to observe a great deal of variability in bowel emptying times, 
which may require many observations and subjects to achieve statistical significance. 
 
Analysis on de-identified data will be performed by study staff. De-Identified data from 
this study may be pooled with data collected by Dr. Bourbeau originating from a similar 
study of the same name currently approved at the Louis Stokes Cleveland DVA Medical 
Center.  
 
5.7 Withdrawal of Subjects 
 
A subject may choose to withdraw from participation in the study at any time. 
There are no potential risks from early withdrawal or removal from the study, as 
this is not a treatment procedure; it is one time feasibility study. They may also 
be withdrawn from the study at any time by the PI or research staff as per the PI’s 
clinical judgement.  
 
6.0 Reporting 
 
 
In the event that the security of VA research-related information (physical or electronic 
data) is compromised, either by unauthorized use, disclosure, transmission, removal, 
theft, loss, or destruction, the PI and authorized research staff will report to the ACOS 
for Research, Privacy Officer, and Information Security Officer within 1 hour, as 
specified in Research & Development Policy 151-17. 
 
7.0 Privacy and Confidentiality 
 
Data Storage 
All study files at the SVAMC will be kept in a locked file in a designated room in the SCI 
unit. Consent forms will be kept in a separate file apart from the data files. All research 
data (physical and electronic) will be anonymized using identifiers supplied by the 
experimenter. In this study, each participant will be assigned a subject number (e.g., 
Subject 001), which will be used to link all data provided by the participant. There will 
be no correspondence between the participant’s subject number and other personally 
identifying information, such as names or contact information, which could link them to 
the study or their data. The subject number key will be locked away separately from any 

 
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data identifiable by subject number. Privacy for patient health information will be 
strictly adhered to by study staff. Information will be collected during an interview in a 
quiet and private area (on the SCI Unit, or in a physician’s private office).  
Because two VA sites will be involved in data analysis (LSCDVAMC and SVAMC), data 
will be transferred between these locations using secure, encrypted VA email to the PI, 
co-PI, or designated research staff. However, nothing beyond data sharing should be 
required between the two sites because they are operating off independent, locally-
approved IRB protocols.  All data shared is de-identified.  
Data Disposal  
In accordance with the VHA Records Control Schedule (RCS 10-1), the official research 
file is a temporary record, which is maintained by VHA for 6 years after cut off of the 
records (cut off being the end of the fiscal year in which the study closed). 
8.0 References 
 
Fact Sheet: VA and Spinal Cord Injury.; 2009. 
www.va.gov/opa/publications/factsheets.asp. 
King RB, Parsons KC, et al. Neurogenic Bowel Management in Adults with Spinal Cord 
Injury.; 1998. 
Anderson KD, Borisoff JF, Johnson RD, Stiens S a, Elliott SL. Long-term effects of 
spinal cord injury on sexual function in men: implications for neuroplasticity. Spinal 
Cord. 2007;45:338-348. 
Anderson KD. Targeting recovery: priorities of the spinal cord-injured population. J 
Neurotrauma. 2004;21(10):1371-1383. 
Fukuda H, Fukai K. The afferent and efferent pathways of the recto-colonic reflex in the 
dog. Jpn J Physiol. 1985;35(5):795-801. 
Chen J-H, Sallam HS, Lin L, Chen JDZ. Colorectal and rectocolonic reflexes in canines: 
involvement of tone, compliance, and anal sphincter relaxation. Am J Physiol Regul 
Integr Comp Physiol. 2010;299(3):R953-9. 
Shafik A, Shafik AA, El-Sibai O, Ahmed I. Role of sympathetic innervation in the 
defecation mechanism: a novel concept of its function. J Spinal Cord Med. 
2003;26(2):150-154. 
Garrett BJR, Howard ER, Jones W. The internal anal sphincter in the cat: A study of 
nervous mechanisms affecting tone and reflex activity. J Physiol. 1974;243:153-166. 
Bouvier M, Gonella J. Nervous control of the internal anal sphincter of the cat. J 
Physiol. 1981;310:457-469. 

 
Page 13 of 13 
 
Ruhl A, Thewiûen M, Ross HG, Cleveland S, Frieling T, Enck P. Discharge patterns of 
intramural mechanoreceptive afferents during selective distension of the cat’s rectum. 
Neurogastroenterol Motil. 1998;10:219-225. 
Sjöqvist A, Hellström PM, Jodal M, Lundgren O. Neurotransmitters involved in the 
colonic contraction and vasodilatation elicited by activation of the pelvic nerves in the 
cat. Gastroenterology. 1984;86(6):1481-1487. 
Takaki M, Neya T, Nakayama S. Functional role of lumbar sympathetic nerves and 
supraspinal mechanism in the defecation reflex of the cat. Acta Med Okayama. 
1987;41(6):249-257. 
Buntzen S, Nordgren S, Delbro D, Hultén L. Reflex interaction from the urinary bladder 
and the rectum on anal motility in the cat. J Auton Nerv Syst. 1995;54:33-40. 
De Groat W, Krier J. An electrophysiological study of the sacral parasympathetic 
pathway to the colon of the cat. J Physiol. 1976;260:425-445. 
De Groat W, Krier J. The sacral parasympathetic reflex pathway regulating colonic 
motility and defaecation in the cat. J Physiol. 1978;276:481-500. 
Frost F, Hartwig D, Jaeger R, Leffler E, Wu Y. Electrical stimulation of the sacral 
dermatomes in spinal cord injury: effect on rectal manometry and bowel emptying. Arch 
Phys Med Rehabil. 1993;74:696-701. 
Shafik A. Recto-colic reflex: role in the defecation mechanism. Int Surg. 81(3):292-294. 
Ng C, Danta M, Prott G, Badcock C-A, Kellow J, Malcolm A. Modulatory influences on 
antegrade and retrograde tonic reflexes in the colon and rectum. Am J Physiol 
Gastrointest Liver Physiol. 2004;287(5):G962-6.