Impact of TTNS on Bladder Symptoms Among People With MS, A RCT

NCT ID: NCT06341673

Last Updated: 2024-04-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-15
• Study Completion Date: 2024-06-30

Brief Summary

Background: Neurogenic lower urinary tract dysfunction is common among people with multiple sclerosis (MS). Recent studies showed that bladder storage symptoms are predominant among MS with a pooled prevalence of frequency at 73.45% followed by urgency at 63.87%. Transcutaneous tibial nerve stimulation (TTNS) is a non-invasive treatment to manage bladder storage symptoms; however, the effectiveness of TTNS is based on a small number of studies with the absence of high-quality evidence. This study aims to investigate the effectiveness of TTNS on bladder storage symptoms compared with sham TTNS among people with MS.Methods: The investigators will use a randomised sham controlled double blind study to explore the effectiveness of TTNS in the treatment of bladder storage symptoms in MS. the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) was followed to standardize the conduct and reporting of the current protocol. The recruitment plan is twofold: 1) Open recruitment for people with MS through King Fahd Hospital of the University communication channels; 2) people with any type of MS attending their routine appointments in MS clinic at King Fahd Hospital of the University, Al Khobar. The investigators will investigate the effectiveness of TTNS compared to sham TTNS on bladder storage symptoms and the effect on quality of life using ICIQ-OAB, ICIQ 3-day bladder diary, ICIQ-LUTS qol, and PSQI. Participant's perception of change post intervention will be evaluated using GPE. Outcomes will be measured at 0, 6 weeks and at 6 months post intervention. A sample size of 72 patients (36 in each group) is required to achieve 90% power with two-tailed tests at an alpha level of 0.05.

Conclusion: Multiple sclerosis is a long-term condition, and self-management is important. TTNS provide a safe, non-invasive intervention that can be administered at home. Should the trial determine that TTNS is effective compared to sham TTNS, the investigators will plan to integrate TTNS into standard clinical care pathways in MS.

Detailed Description

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) mainly affects young individuals. The mechanism responsible for MS initiates with the formation of acute inflammatory lesions categorized by breakdown of the blood-brain barrier (BBB) that causes scattered lesions in the brain and spinal cord , and it is the leading cause of autonomic dysfunction MS is increasingly a universal disease reported by joint project of the Multiple Sclerosis International Federation and the World Health Organization report . MS is more common in females than males with gender distribution ratio of 2.7:1. Likewise, the female: male ratio appears to be 3:1 in most developed countries.

The International Continence Society defines neurogenic lower urinary tract dysfunction (NLUTD) as lower urinary tract symptoms following neurological disease. The range and severity of neurogenic bladder symptoms depend on the location of the neurologic lesions, with more definite symptoms in people with MS associated with lesions at the pontine micturition centre (PMC) causing bladder storage symptoms and/ or the supra sacral lesions resulting in both bladder storage and voiding symptoms accompanied with an increased post-void residual. According to ICS classification of lower urinary tract symptoms terminology, bladder storage symptoms are a combination of urinary frequency, urinary urgency, nocturia, with or without urge urinary incontinence. Recent publication showed that bladder storage symptoms are the predominant symptoms among people with MS with an estimated pooled prevalence of frequency at 73.45% followed by urgency at 63.87%.

Several studies have reported the negative impacts of NLUTD on quality of life (QoL) among MS population including psychological distress, sleep disturbances, barriers to engaging in physical and social activities and disturbances of daily living. Previous studies showed the relationship between sleep disturbances and urinary symptoms. Also, sleep disturbance is associated with more severe urinary incontinence and overactive bladder symptoms. However, to date no studies have investigated the association of bladder storage symptoms and sleep disturbances among PwMS and bladder storage system and the possible impact of TTNS on quality of sleep among PwMS and bladder storage symptoms. Early diagnosis and proper management are of utmost importance in preserving good QoL among people with MS and urinary symptoms.

Management of bladder storage symptoms for neurogenic bladder population comprise pharmacological and non-pharmacological interventions. According to European Association of Urology (EAU), pharmacologic interventions include antimuscarinic which is considered as a first line intervention and Intradetrusor onabotulinumtoxin A (BOTOX) injections as a second-line treatment intervention. Non-pharmacologic interventions include patient education, life style modifications, behavioural interventions, pelvic floor muscle training (PFMT), and/ or neuromodulations. Tibial nerve stimulation (TNS) is a form of neuromodulation used to inhibit overactivity of detrusor muscle by using either a needle electrode (percutaneous tibial nerve stimulation) (PTNS), or adhesive pads (transcutaneous tibial nerve stimulation) (TTNS).

A number of small-scale studies demonstrate that tibial nerve stimulation (TTNS) may be a promising management approach for bladder storage symptoms in non-neurogenic and neurogenic bladder populations with the need of high quality studies to assess the effectiveness of this intervention. The exact mechanism by which TNS potentially treats bladder control is not yet fully understood.

To date no randomized controlled trials (RCT's) have been identified that explore the impact of TTNS on bladder storage symptoms, activity limitations and participation restrictions in people with MS. RCT's are required to provide a strong evidence-base for using TTNS among neurogenic bladder storage symptoms in MS. Recent publication of single-arm feasibility study showed that TTNS is feasible, safe, and acceptable as a treatment of bladder storage symptoms among PwMS. Therefore, there is a need to conduct RCTs using standardized reporting of outcome measures administering, widely available and affordable device, the transcutaneous electrical nerve stimulation (TENS) unit. In the current study the investigators chose the sham comparator to assess the efficacy of TTNS on bladder storage symptoms in MS population. Sham intervention enable to reduce uncertainty regarding the causal relationship between an intervention and outcome, also it is suitable in the beginning phases of efficacy-exploratory research when it is still unknown whether the given treatment has any effect.

Conditions

Overactive Bladder Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Active arm: Transcutaneous Electrical Nerve Stimulation- Transcutaneous Tibial Nerve Stimulation

Participants will useTENS to stimulate tibial nerve on the medial side of the foot for 6 weeks, a total of 18 sessions, three times weekly for 30 minutes per session. All TENS units will be programmed and locked by principal investigator to ensure fixed stimulation parameters are used among participants throughout the study intervention. The stimulation frequency will be set at 10 Hz with a pulse duration 200 μs. Participants will be advised to apply the stimulation in a supine position or supported sitting with extended legs to avoid compression of nerve roots at the knee joint. Participants will place the stimulation electrode, the negative electrode, between 5 and 10 cm above the medial malleolus and the positive electrode behind the left medial malleolus.

Group Type: ACTIVE_COMPARATOR

Active Transcutaneous Electrical Nerve Stimulation (TENS)

Intervention Type: DEVICE

For active group: TENS is to be used to stimulate tibial Nerve at medial aspect of the foot. The stimulation is proved by flexion of the big toe (motor response) and/or tingling sensation of ipsilateral sole of foot (sensory response) by raising the current amplitude, mA, intensity. Increasing the intensity above sensory threshold is recommended but should not be painful

Sham arm: Transcutaneous Electrical Nerve Stimulation

Participants randomized to the sham group, will place the TENS on the lateral side of the foot, the negative electrode on the top of the foot just above the small toe for conduction and the positive electrode on the bottom of below the smallest toe to avoid the tibial nerve and relevant cutaneous nerves. The location of conduction electrode was chosen since this location is proved to be away from bladder, pelvic, or major organ nerve acupuncture pathway. Participants will be instructed to raise up the intensity until the first and slight tingling sensation on the sole of the foot or toe. The stimulation will be used for 6 weeks, a total of 18 sessions, three times weekly for 30 minutes per session.

Group Type: SHAM_COMPARATOR

Sham Transcutaneous Electrical Nerve Stimulation (TENS)

Intervention Type: DEVICE

TENS on the lateral side of the foot, the negative electrode on the top of the foot just above the small toe for conduction and the positive electrode on the bottom of below the smallest toe to avoid the tibial nerve and relevant cutaneous nerves. Participants will be instructed to raise up the intensity until the first and slight tingling sensation on the sole of the foot or toe

Interventions

Active Transcutaneous Electrical Nerve Stimulation (TENS)

For active group: TENS is to be used to stimulate tibial Nerve at medial aspect of the foot. The stimulation is proved by flexion of the big toe (motor response) and/or tingling sensation of ipsilateral sole of foot (sensory response) by raising the current amplitude, mA, intensity. Increasing the intensity above sensory threshold is recommended but should not be painful

Intervention Type: DEVICE

Sham Transcutaneous Electrical Nerve Stimulation (TENS)

TENS on the lateral side of the foot, the negative electrode on the top of the foot just above the small toe for conduction and the positive electrode on the bottom of below the smallest toe to avoid the tibial nerve and relevant cutaneous nerves. Participants will be instructed to raise up the intensity until the first and slight tingling sensation on the sole of the foot or toe

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Ambulatory (with or without assistive device)
• Aged ≥18 years old
• Able to understand spoken and written Arabic Language
• Self-reported with at least one bladder storage symptom such as urinary frequency urinary urgency, nocturia, with or without urge urinary incontinence
• Willing to give written informed consent
• Able to understand how to complete the study outcome measures

Exclusion Criteria

People with MS will be excluded if they have one or more of the following criteria at randomization:

• Indwelling urethral catheter
• Indwelling suprapubic catheter
• Bladder malignancy
• Diabetic mellitus
• Pregnant women or plan to be pregnant during the study intervention
• Recent pelvic related surgery <1 year
• Pacemaker or other metallic internal devices
• Urinary tract infections (UTIs) during recruitment phase
• Unable to understand the instructions relating to operating the unit
• Having a bladder BOTOX-injection in the last 12-month

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hawra Al-Dandan

OTHER

Sponsor Role: lead

Responsible Party

Hawra Al-Dandan

Senior specialist

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Dr Hawra AL Dandan, PhD

Role: PRINCIPAL_INVESTIGATOR

Imam Abdulrahman Bin Faisal University

Locations

King Fahd Hospital of the University

Khobar, Eastern Providence, Saudi Arabia

Site Status: RECRUITING

Countries

Saudi Arabia

Central Contacts

Dr Hawra Al Dandan, PhD

Role: CONTACT

hdandan@iau.edu.sa

+966555901977

Dr Saad Al Saadi, PhD

Role: CONTACT

ssaadi@iau.edu.sa

Facility Contacts

Dr Hawra Al Dandan, PhD

Role: primary

hdandan@iau.edu.sa

+966555901977

Dr Saad Al Saadi, PhD

Role: backup

ssaadi@iau.edu.sa

+966552519515

Other Identifiers

IRB-2023-O3-442

Identifier Type: -

Identifier Source: org_study_id