## Protocol Section
### Identification Module
**NCT ID:** NCT06416878

**Acronym:** BESCES

**Brief Title:** Brief ES for Recovery of Autonomic Function in CES

**Official Title:** Can Brief Perioperative Epidural Electrical Stimulation Improve Recovery of Autonomic Function in Cauda Equina Syndrome

#### Organization Study ID Info
**ID:** UoL001787
#### Organization
**Class:** OTHER
**Full Name:** University of Liverpool
### Status Module
#### Completion Date
**Date:** 2025-09-15

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-15

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-09-15

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-02-15

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-01-08
**Study First Submit QC Date:** 2024-05-15
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Liverpool

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** BESCES is a study that aims to explore the feasibility of intraoperative brief epidural electrical stimulation (ES) for patients undergoing routine decompression for cauda equina syndrome. In consenting patients, brief ES will be applied using a CE-marked SCS trial kit once sufficient decompression is achieved. In participants who do not recover function following decompression, brief post-op ES will be applied to see if can facilitate micturition and/or removal of the catheter.

The study will assess:

The feasibility of intervention. If brief ES can facilitate conduction in residual neurons. If brief ES can facilitate neuronal recovery

**Detailed Description:** Cauda equina syndrome (CES), defined as a compression of nerves controlling bowel, bladder and sexual function due to lumbar disc prolapse has a prevalence of 2 per 100,000 UK population per year. It mostly affects individuals 30-49 years of age. Emergency surgery to decompress the nerves is the mainstay of treatment. Despite adequate decompression, 17% of patients are left incontinent and 50% experience persistent bowel, bladder or sexual dysfunction needing long-term supportive symptomatic management and compromising their social cohesion and economic productivity.

Theoretically, there are two possible ways of improving these functions - improving regeneration of damaged cells and improving conduction in partially damaged/residual cells. The use of perioperative electrical stimulation (ES) has shown significant promise in facilitating recovery in peripheral nerve compression syndromes. Epidural stimulation is routinely used for treating neuropathic pain and there is anecdotal evidence of improved bladder and bowel function in patients with CES who have received epidural spinal cord stimulation for chronic pain.

The overall aim of this feasibility study is to determine if a full definitive RCT is possible. The investigators want to see if it is possible to timely and safely deliver epidural stimulation in patients presenting with bowel, bladder or sexual dysfunction due to cauda equina compression, undergoing emergency lumbar decompression, assess the potential effect size of brief post-decompression ES proximal to the level of compression in facilitating axonal regeneration to support further RCT. The investigators also want to see if brief ES can improve conduction in residual neurons.

40 patients presenting with CES shall be enrolled. At the time of decompression surgery, consenting patients shall receive ES. With standard care, patients who still have symptoms after decompression, remain symptomatic at 1 year. Comparison of functional outcomes post-surgery and at 3, 6 and 12 months will enable assessment of recovery due to axonal regeneration.

Results shall assess the safety and feasibility of doing the study in emergency settings - enrolment and consent issues and assess effect size, this will provide sufficient information and, if successful, will lead to a definitive Randomised Control Trial (RCT).

### Conditions Module

**Conditions:**

- Cauda Equina Syndrome

**Keywords:**

- cauda equina syndrome

- electrical stimulation

- spinal cord stimulator

- recovery of autonomic function

- axonal regeneration

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** Consecutive patients presenting to neurosurgical department with acute cauda equina syndrome with autonomic dysfunction.

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 40

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** All participants

**Intervention Names:**

- Device: Brief ES at the time of decompression for cauda equina syndrome

- Device: Brief ES to facilitate mcturition/removal of catheter

**Label:** Intervention

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Intervention

**Description:** In patients operated for acute cauda equina syndrome with autonomic dysfunction epidural ES will be delivered utilising SCS trial electrode. It will be delivered for 10 minutes caudal to compression site and for 60 mins cranial to compression site while the wound is closed and patient recovered.

**Name:** Brief ES at the time of decompression for cauda equina syndrome

**Type:** DEVICE

#### Intervention 2

**Arm Group Labels:**

- Intervention

**Description:** In patients who do not fully recover function following decompression, brief ES will be applied before second micturition attempt.

**Name:** Brief ES to facilitate mcturition/removal of catheter

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** Recruitment rate of 50% or above will be considered sufficient for feasibility of conducting future RCT.

**Measure:** Recruitment Rate

**Time Frame:** 6 months

**Description:** In participants who do not recover autonomic function, Pudendal Nerve SEP will be performed to assess baseline conduction in residual neurons and recovery rate. Results at 3 months will be compared against baseline.

**Measure:** Pudendal Somatosensory Evoked Potentials (SEP) - amplitude (uV)

**Time Frame:** Post-operatively and at 3 months.

**Description:** In participants who do not recover autonomic function, Pudendal Nerve SEP will be performed to assess baseline conduction in residual neurons and recovery rate. Results at 3 months will be compared against baseline.

**Measure:** Pudendal Somatosensory Evoked Potentials (SEP) - latency (ms)

**Time Frame:** Post-operatively and at 3 months.

**Description:** Intraoperative stimulation parameters will be set to the motor threshold - visually assessed motor response to stimulation. Post-operative stimulation parameters will be set according to patients response - sensation of motor contraction or paraesthesia. Default frequency is 20 Hz and can be modified in 10Hz increments. Descriptive analysis of these parameters shall enable optimisation of settings in future studies.

**Measure:** Stimulation parameters - Frequency (Hz)

**Time Frame:** At the time of the surgery and immediately post-op

**Description:** Intraoperative stimulation parameters will be set to the motor threshold - visually assessed motor response to stimulation. Post-operative stimulation parameters will be set according to patients response - sensation of motor contraction or paraesthesia. Amplitude is increased in 0.1mA increments until response is ascertained. Maximal safe amplitude is considered to be 15mA. Descriptive analysis of these parameters shall enable optimisation of settings in future studies.

**Measure:** Stimulation parameters - Amplitude (mA)

**Time Frame:** At the time of the surgery and immediately post-op

**Description:** Intraoperative stimulation parameters will be set to the motor threshold - visually assessed motor response to stimulation. Post-operative stimulation parameters will be set according to patients response - sensation of motor contraction or paraesthesia. Default pulse width is 100 microseconds and it can be adjusted in 10 microsecond increments. Descriptive analysis of these parameters shall enable optimisation of settings in future studies.

**Measure:** Stimulation parameters - Pulse width (microseconds)

**Time Frame:** At the time of the surgery and immediately post-op

#### Secondary Outcomes

**Description:** The SFIQ consists of 5 items. Items 1 and 5 are Yes/No questions. Item 2 is an 8-question scale with answers ranging from 0 (best) to 3 (worst) each. Item 3 is a scale ranging from 1 (best) to 8 (worst). Item 4 is a scale ranging from 1 (best) to 6 (worst).

**Measure:** Short Form Incontinence Questionnaire (SFIQ)

**Time Frame:** On admission and at 3, 6 and 12 months.

**Description:** The ASEX consists of 5 questions with answers from 1 (best) to 6 (worst)

**Measure:** Arizona Sexual Experiences Scale (ASEX)

**Time Frame:** On admission and at 3, 6 and 12 months.

**Description:** NBD is a 10-question item with a score range from 0 (best) to 47 (worst). A score of 0-6 is considered very minor, 7-9 minor, 10-13 moderate and 14+ severe.

**Measure:** Neurogenic Bowel Dysfunction (NBD) Questionnaire

**Time Frame:** On admission and at 3, 6 and 12 months.

**Description:** The ODI assesses disability related to back pain. It is a 10-question item, each scored from 0 (best) to 5 (worst). The total score is between 0 (best) and 50 (worst).

**Measure:** Oswestry Disability Index (ODI)

**Time Frame:** On admission and at 3, 6 and 12 months.

**Description:** Rand Short Form Health Survey (SF-36) is a 36-question tool, developed at RAND as part of the Medical Outcomes Study. It assesses the quality of life in 9 categories (Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Energy/fatigue, Emotional well-being, Social functioning, Pain, General health, Health change). Each category is scored from 0% (worst) to 100% (best).

**Measure:** Rand SF-36 Questionnaire

**Time Frame:** On admission and at 3, 6 and 12 months.

**Description:** PVBS assesses post-micturition bladder volume. Volume above 200mL suggests incomplete bladder emptying or retention. Trends in PVBS will be assessed post-operatively and at 3-month follow-up in patients with incomplete recovery following the surgery.

**Measure:** Post-void bladder scan (PVBS)

**Time Frame:** At baseline, post-operative (x3) and at 3 months.

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Age \>18.
* Cauda equina syndrome with bladder, bowel or sexual dysfunction (CES-I or CES-R) secondary to acute lumbar disc prolapse.
* Selected for emergency surgery.

Exclusion Criteria:

* No bladder, bowel or sexual dysfunction (Only bilateral radicular symptoms).
* Previous spinal surgery with risk of adhesions.
* Multilevel degeneration with inadequate safe space to pass epidural electrode.
* Pre-existent bladder, bowel or sexual dysfunction.
* History of peripheral neuropathy.
* Contraindications to neurostimulation (e.g. pacemaker, immune deficiency, uncontrolled diabetes, sepsis, active pressure sore, spinal cord stimulator in situ).
* Intraoperative CSF leak.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Rafal.Szylak@nhs.net

**Name:** Rafal A Szylak, MBBS eq.

**Phone:** 0151 525 3611

**Phone Ext:** 64124

**Role:** CONTACT

**Contact 2:**

**Email:** Deepti.Bhargava@nhs.net

**Name:** Deepti Bhargava, MD

**Phone:** 0151 525 3611

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Liverpool

**Contacts:**

***Contact 1:***

- **Email:** rafal.szylak@nhs.net

- **Name:** Rafal Szylak, MBBS

- **Phone:** 0044 151 525 3611

- **Role:** CONTACT

**Country:** United Kingdom

**Facility:** The Walton Centre NHS Foundation Trust

**State:** Merseyside

**Status:** RECRUITING

**Zip:** L9 7LJ

#### Overall Officials

**Official 1:**

**Affiliation:** University of Liverpool

**Name:** Andrew Marshall, PhD

**Role:** STUDY_CHAIR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Al-Majed AA, Neumann CM, Brushart TM, Gordon T. Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J Neurosci. 2000 Apr 1;20(7):2602-8. doi: 10.1523/JNEUROSCI.20-07-02602.2000.

**PMID:** 10729340

**Citation:** Gordon T, Amirjani N, Edwards DC, Chan KM. Brief post-surgical electrical stimulation accelerates axon regeneration and muscle reinnervation without affecting the functional measures in carpal tunnel syndrome patients. Exp Neurol. 2010 May;223(1):192-202. doi: 10.1016/j.expneurol.2009.09.020. Epub 2009 Oct 1.

**PMID:** 19800329

**Citation:** Juckett L, Saffari TM, Ormseth B, Senger JL, Moore AM. The Effect of Electrical Stimulation on Nerve Regeneration Following Peripheral Nerve Injury. Biomolecules. 2022 Dec 12;12(12):1856. doi: 10.3390/biom12121856.

**PMID:** 36551285

**Citation:** Power HA, Morhart MJ, Olson JL, Chan KM. Postsurgical Electrical Stimulation Enhances Recovery Following Surgery for Severe Cubital Tunnel Syndrome: A Double-Blind Randomized Controlled Trial. Neurosurgery. 2020 Jun 1;86(6):769-777. doi: 10.1093/neuros/nyz322.

**PMID:** 31432080

**Citation:** Wong JN, Olson JL, Morhart MJ, Chan KM. Electrical stimulation enhances sensory recovery: a randomized controlled trial. Ann Neurol. 2015 Jun;77(6):996-1006. doi: 10.1002/ana.24397. Epub 2015 May 4.

**PMID:** 25727139

**Citation:** Barber B, Seikaly H, Ming Chan K, Beaudry R, Rychlik S, Olson J, Curran M, Dziegielewski P, Biron V, Harris J, McNeely M, O'Connell D. Intraoperative Brief Electrical Stimulation of the Spinal Accessory Nerve (BEST SPIN) for prevention of shoulder dysfunction after oncologic neck dissection: a double-blinded, randomized controlled trial. J Otolaryngol Head Neck Surg. 2018 Jan 23;47(1):7. doi: 10.1186/s40463-017-0244-9.

**PMID:** 29361981

**Citation:** Rascon-Ramirez FJ. Spinal cord stimulation and cauda equina syndrome: Could it be a valid option? A report of two cases. Neurocirugia (Astur : Engl Ed). 2021 Feb 5:S1130-1473(21)00003-8. doi: 10.1016/j.neucir.2020.12.002. Online ahead of print. English, Spanish.

**PMID:** 33558146

**Citation:** Sayanagi J, Acevedo-Cintron JA, Pan D, Schellhardt L, Hunter DA, Snyder-Warwick AK, Mackinnon SE, Wood MD. Brief Electrical Stimulation Accelerates Axon Regeneration and Promotes Recovery Following Nerve Transection and Repair in Mice. J Bone Joint Surg Am. 2021 Oct 20;103(20):e80. doi: 10.2106/JBJS.20.01965.

**PMID:** 34668879

**Citation:** Woodfield J, Hoeritzauer I, Jamjoom AAB, Jung J, Lammy S, Pronin S, Hannan CJ, Watts A, Hughes L, Moon RDC, Darwish S, Roy H, Copley PC, Poon MTC, Thorpe P, Srikandarajah N, Grahovac G, Demetriades AK, Eames N, Sell PJ, Statham PFX; UCES Collaborators; British Neurosurgical Trainee Research Collaborative. Presentation, management, and outcomes of cauda equina syndrome up to one year after surgery, using clinician and participant reporting: A multi-centre prospective cohort study. Lancet Reg Health Eur. 2022 Nov 17;24:100545. doi: 10.1016/j.lanepe.2022.100545. eCollection 2023 Jan.

**PMID:** 36426378

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004194

- Term: Disease

- ID: D000010335

- Term: Pathologic Processes

- ID: D000019121

- Term: Burkholderia Infections

- ID: D000016905

- Term: Gram-Negative Bacterial Infections

- ID: D000001424

- Term: Bacterial Infections

- ID: D000001423

- Term: Bacterial Infections and Mycoses

- ID: D000007239

- Term: Infections

- ID: D000009408

- Term: Nerve Compression Syndromes

- ID: D000010523

- Term: Peripheral Nervous System Diseases

- ID: D000009468

- Term: Neuromuscular Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000011129

- Term: Polyradiculoneuropathy

- ID: D000011115

- Term: Polyneuropathies

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC01

- Name: Infections

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: HIGH

- As Found: Syndrome

- ID: M9008

- Name: Glanders

- Relevance: HIGH

- As Found: Equina

- ID: M1874

- Name: Cauda Equina Syndrome

- Relevance: HIGH

- As Found: Cauda Equina Syndrome

- ID: M10283

- Name: Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M21130

- Name: Burkholderia Infections

- Relevance: LOW

- As Found: Unknown

- ID: M4722

- Name: Bacterial Infections

- Relevance: LOW

- As Found: Unknown

- ID: M19249

- Name: Gram-Negative Bacterial Infections

- Relevance: LOW

- As Found: Unknown

- ID: M12136

- Name: Mycoses

- Relevance: LOW

- As Found: Unknown

- ID: M4721

- Name: Bacterial Infections and Mycoses

- Relevance: LOW

- As Found: Unknown

- ID: M12352

- Name: Nerve Compression Syndromes

- Relevance: LOW

- As Found: Unknown

- ID: M5853

- Name: Charcot-Marie-Tooth Disease

- Relevance: LOW

- As Found: Unknown

- ID: M18092

- Name: Hereditary Sensory and Motor Neuropathy

- Relevance: LOW

- As Found: Unknown

- ID: M13432

- Name: Peripheral Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12411

- Name: Neuromuscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14013

- Name: Polyradiculoneuropathy

- Relevance: LOW

- As Found: Unknown

- ID: M13999

- Name: Polyneuropathies

- Relevance: LOW

- As Found: Unknown

- ID: T2505

- Name: Glanders

- Relevance: HIGH

- As Found: Equina

- ID: T1015

- Name: Cauda Equina Syndrome

- Relevance: HIGH

- As Found: Cauda Equina Syndrome

- ID: T1081

- Name: Charcot-Marie-Tooth Disease

- Relevance: LOW

- As Found: Unknown

- ID: T2761

- Name: Hereditary Motor and Sensory Neuropathy

- Relevance: LOW

- As Found: Unknown

- ID: T2766

- Name: Hereditary Neuropathy With Liability to Pressure Palsies

- Relevance: LOW

- As Found: Unknown

- ID: T5067

- Name: Roussy Levy Syndrome

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000005896

- Term: Glanders

- ID: D000077684

- Term: Cauda Equina Syndrome

- ID: D000013577

- Term: Syndrome

### Misc Info Module

- Version Holder: 2024-05-31
