The Effect of Bilateral Transcutaneous Tibial Nerve Stimulation on Symptoms of Chronic Functional Constipation by Evaluation of Parasympathetic System through Hemodynamic Monitoring and Salivary Acetylcholinesterase Biomarker
To evaluate the effect of bilateral transcutaneous tibial nerve stimulation on symptoms and quality of life in individuals with chronic functional constipation by assessing parasympathetic activity and comparing it with conventional pelvic floor physiotherapy.
Design
A single-blind, randomized clinical trial involving two groups of 15 patients (control and intervention ), utilizing simple randomization through a lottery-based allocation method.
Settings and conduct
Volunteers are randomly assigned to control or intervention groups, blinded to treatment type. Both groups receive CPFP three times weekly for six weeks at Iran University of Medical Sciences. The intervention group will also undergo daily home-based BTTNS. WCSS (Wexner constipation scoring system) and PAC-QOL questionnaires will be completed at baseline, mid-treatment, and post-treatment to assess symptoms and quality of life. Parasympathetic activity and hemodynamic parameters will be measured via salivary acetylcholinesterase, blood pressure, and heart rate variability.
Participants/Inclusion and exclusion criteria
Inclusion criteria:
Female aged 20 to 60 years meeting Rome III criteria for chronic functional constipation
Exclusion criteria:
Presence of an organic pathology for constipation, neurological diseases, peripheral neuropathies, congenital anorectal malformations, anatomical abnormalities requiring surgery، major depression, pregnancy or periodontal disease
Intervention groups
Control group: receiving conventional pelvic floor physiotherapy (CPFP)
Intervention group: receiving a combination of conventional pelvic floor physiotherapy and bilateral transcutaneous tibial nerve stimulation (TTNS)
Main outcome variables
1. Clinical symptoms of chronic constipation
2. Quality of life
3. Hemodynamic parameters
4. Salivary acetylcholinesterase levels
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20250812066839N1
Registration date:2025-08-26, 1404/06/04
Registration timing:prospective
Last update:2025-08-26, 1404/06/04
Update count:0
Registration date
2025-08-26, 1404/06/04
Registrant information
Name
Parnian Mirbehresi
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 2222 2059
Email address
pbehresi@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2025-09-11, 1404/06/20
Expected recruitment end date
2026-01-05, 1404/10/15
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The Effect of Bilateral Transcutaneous Tibial Nerve Stimulation on Symptoms of Chronic Functional Constipation by Evaluation of Parasympathetic System through Hemodynamic Monitoring and Salivary Acetylcholinesterase Biomarker
Public title
Tibial Nerve Stimulation in Chronic Functional Constipation
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Female participants aged 20 to 60 years who meet the Rome III criteria for chronic functional constipation
Exclusion criteria:
Currently receiving any other treatment for chronic functional constipation
Previous treatment for chronic functional constipation within the past month
Presence of any organic disorder known to cause constipation
Diagnosis of neurological disorders (multiple sclerosis, Parkinson’s disease, or spinal cord injury)
Presence of diabetic neuropathy
Presence of congenital anomalies of the anorectal region
Presence of anatomical disorders requiring surgical intervention (mucosal prolapse, rectocele, cystocele) as determined by a specialist
Suffering from major depression (Beck Depression Inventory score > 30)
Use of medications known to induce constipation (e.g., antidepressants, antihistamines, antiepileptic drugs)
Previous anorectal surgery
Current pregnancy or intention to become pregnant
Prescence of periodontal disease
Age
From 20 years old to 60 years old
Gender
Female
Phase
N/A
Groups that have been masked
Participant
Data analyser
Sample size
Target sample size:
30
Randomization (investigator's opinion)
Randomized
Randomization description
The randomization method will be based on simple random allocation rule through lottery-based method. Specifically, 15 balls labeled “A” (control group) and 15 balls labeled “B” (intervention group) will be placed in a container and then drawn one at a time without replacement. The sequence of drawn balls will be recorded, creating a random allocation sequence.
Blinding (investigator's opinion)
Single blinded
Blinding description
Participants will be randomly assigned, without their knowledge, to either the control or intervention group. Accordingly, none of the participants will be aware of the existence of two treatment arms. Additionally, data analysts will remain blinded to group allocation (control vs. intervention) throughout the analysis process.
Placebo
Not used
Assignment
Factorial
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research Ethics Committees of Iran University of Medical Sciences
Street address
School of Rehabilitation Science, Nezam Ave, Mirdamad Ave, Tehran,
City
Tehran
Province
Tehran
Postal code
1545913487
Approval date
2024-09-03, 1403/06/13
Ethics committee reference number
IR.IUMS.REC.1403.495
Health conditions studied
1
Description of health condition studied
Functional Constipation
ICD-10 code
K59.0
ICD-10 code description
Constipation
Primary outcomes
1
Description
Salivary acetylcholine esterase
Timepoint
Baseline (prior to intervention), midpoint, and end of study
Method of measurement
Collection of unstimulated saliva sample and analysis using an acetylcholinesterase assay kit.
2
Description
Hear Rate Variability
Timepoint
Baseline (prior to intervention), midpoint, and end of study
Method of measurement
Electrocardiography
Secondary outcomes
1
Description
Clinical symptoms of chronic functional constipation
Timepoint
Baseline (prior to intervention), midpoint, and end of study
Method of measurement
Wexner constipation scoring system questionnaire
2
Description
Quality of life
Timepoint
Baseline (prior to intervention), midpoint, and end of study
Method of measurement
Patient Assessment of Constipation-Quality of Life questionnaire
Intervention groups
1
Description
Control group: Participants will receive conventional pelvic floor physiotherapy, which includes biofeedback using a rectal electrode for retraining and strengthening the anorectal muscles, prescription of pelvic floor muscle stretching and strengthening exercises, diaphragmatic breathing instruction, and bowel behavioral therapy. Treatment sessions will be conducted three times per week over a six-week period.
Category
Rehabilitation
2
Description
Intervention group: The intervention will consist of two components initiated concurrently: conventional pelvic floor physiotherapy and tibial nerve electrical stimulation. Conventional pelvic floor physiotherapy includes biofeedback using a rectal electrode for retraining and strengthening the anorectal muscles, prescription of pelvic floor muscle stretching and strengthening exercises, diaphragmatic breathing instruction, and bowel behavioral therapy. Treatment sessions will be conducted three times per week over a six-week period. Tibial nerve electrical stimulation will be administered via a home-use electrical stimulation device for 30 minutes each morning upon waking, continued daily for six weeks.
Category
Rehabilitation
Recruitment centers
1
Recruitment center
Name of recruitment center
Hazrat Rasul Akram educational, research and treatment complex
Full name of responsible person
Parnian Mirbehresi
Street address
Hospital of Hazrat Rasool Akram, Mansouri Street, Niyaish Street, Satarkhan
City
Tehran
Province
Tehran
Postal code
1445613131
Phone
+98 21 6435 1243
Email
rasoolhospital@iums.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Iran University of Medical Sciences
Full name of responsible person
Afsoon Hassani Mehraban
Street address
Faculty of Rehabilitation Sciences, Iran University of Medical Sciences, Shah Nazari Street, Mirdamad, Madar Square, Tehran
City
Tehran
Province
Tehran
Postal code
1546913487
Phone
+98 21 2222 2059
Email
mehraban.a@iums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Iran University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Iran University of Medical Sciences
Full name of responsible person
Parnian Mirbehresi
Position
PhD Candidate
Latest degree
Master
Other areas of specialty/work
Physiotherapy
Street address
Faculty of Rehabilitation Sciences, Iran University of Medical Sciences, Shah Nazari Street, Mirdamad, Madar Square, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1545913487
Phone
+98 21 2222 2059
Fax
Email
pbehresi@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Iran University of Medical Sciences
Full name of responsible person
Parnian Mirbehresi
Position
PhD Candidate
Latest degree
Master
Other areas of specialty/work
Physiotherapy
Street address
Faculty of Rehabilitation Sciences, Iran University of Medical Sciences, Shah Nazari Street, Mirdamad, Madar Square, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1545913487
Phone
+98 21 2222 2059
Fax
Email
pbehresi@gmail.com
Person responsible for updating data
Contact
Name of organization / entity
Iran University of Medical Sciences
Full name of responsible person
Parnian Mirbehresi
Position
PhD Candidate
Latest degree
Master
Other areas of specialty/work
Physiotherapy
Street address
Faculty of Rehabilitation Sciences, Iran University of Medical Sciences, Shah Nazari Street, Mirdamad, Madar Square, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1545913487
Phone
+98 21 2222 2059
Fax
Email
pbehresi@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available