Sham-Controlled RCT on 10kHz High-Frequency Spinal Cord Stimulation for Chronic Neuropathic Low Back Pain (Modulate-LBP) (Modulate-LBP)

Multicentre, Double Blind, Randomised Sham-Controlled Trial of 10kHz High-Frequency Spinal Cord Stimulation for Chronic Neuropathic Low Back Pain (Modulate-LBP)

Multicentre, randomised, double-blinded, sham-controlled trial with parallel economic evaluation. Patients will be allocated 1:1 to activated 10kHz SCS plus usual care (intervention) or sham 10kHz SCS plus usual care (control) and followed up to 6 months.

Study Overview

• Status: Unknown
• Conditions: Chronic Low Back Pain; Neuropathic Pain; Refractory Pain
• Intervention / Treatment: Device: Nevro Senza System (HF10 Therapy)

Detailed Description

The prevalence of chronic low back pain in the population is estimated to range between at 12% and 28% (1-4). Within this group an estimated 12-15% of adults suffer from chronic neuropathic lower back pain (CNLBP), have relatively greater pain severity, and account for more of the costs of this condition (5,6). This subgroup of people with CNLBP are the focus of the proposed trial.

The National Institute for Health and Care Excellence (NICE) recommends SCS for refractory neuropathic pain (TA159) (7). It is routinely used for people with predominant, neuropathic, radicular pain typically resulting from, or persisting after, spinal surgery (so-called failed back surgery syndrome (FBSS) (8-10). SCS has been shown to be cost effective for this indication (11).

Conventional SCS consists of the insertion of a medical wire (lead) introduced into the epidural space through a needle puncture. The lead is then positioned to target the pain by passing current into the lead from an external power source to generate a pins and needles sensation (paraesthesias) over the painful area. Analgesia occurs when the paraesthesia overlaps and therefore masks the painful area. Once pain reduction is demonstrated, the battery is implanted under the skin of the abdomen, flank or buttock. SCS is most commonly used in the treatment of leg pain of FBSS. However, due to lack of existing evidence and the difficulty of obtaining paraesthesia over the low back, SCS has traditionally not been recommended for treating patients with back pain without previous back surgery (10, 12).

High frequency 10kHz-SCS is a recent major advance in SCS technology. The current is delivered at 10kHz frequency as opposed to the 40 to 60Hz generated by the conventional SCS (13). The key advantages of a higher frequency current are:

10kHz-SCS has been shown to be superior (14) to conventional SCS in targeting residual low back pain following back surgery. Moreover, it does not generate any stimulation related sensations or paraesthesia so is preferred by patients as they are saved from needing to experience these distracting and occasional shocking sensations of conventional SCS. Therefore, 10kHz-SCS allows to smoothly conduct sham controlled or double blind studies in the field of SCS without the need for device modifications.

The lead applicant conducted an uncontrolled, multicentre, single arm study with 83 people with significant low back pain with or without leg pain, implanted with a 10kHz-SCS. At 24 months, the mean reported VAS score for back pain was 3.3 (SD 0.3), compared with 8.4 (SD 0.1) at baseline (pre-implant) and 2.7 (SD 0.3) at 6 months with 60% of subjects reporting >50% back pain relief. Similar improvements were observed in leg pain, disability, sleep and marked reductions in medication intake (15).

In a more recent multicentre RCT, 10kHz-SCS therapy demonstrated superiority to conventional low-frequency SCS in the treatment of post-surgical neuropathic pain. A total of 198 subjects with both back and leg pain were randomised in a 1:1 ratio to a 10 KHz-SCS or conventional SCS. 10kHz-SCS decreased back pain intensity by 67% compared to 44% in the conventional SCS arm (16). This decrease was sustained at 24 months (17).

The above mentioned studies focused on neuropathic back pain in the context of patients with previous spinal surgery. However, a small subset of patients without prior spine surgery that received 10kHz-SCS therapy in both these studies have shown good pain relief and functional improvements in both studies comparable to those with FBSS (14,16).

The investigators hypothesised that patients with CNLBP with no prior spine surgery would benefit from 10kHz-SCS. To evaluate this hypothesis, the investigators initially designed and conducted an open label uncontrolled pilot study in 21 patients with CNLBP and no prior spine surgery. 10kHz-SCS therapy significantly reduced back pain intensity by an average of 5.59 (SD 1.80) (-72.6% vs baseline) at 12 months in medically refractory low back pain patients with no past history of spine surgery. 90% of the implanted patients were classified as responders (i.e. VAS back pain reduction >50%) at 12 months. The investigators also observed a significant increase in physical function scores and health-related quality of life at one year post 10kHz-SCS implant. Mean pain intensity was reduced by 73% and disability measured by the Oswestry Disability Index was reduced by 48%. Opioid medication intake decreased by 64% and mean EQ-5D quality of life scores improved from 0.16 to 0.47. More importantly 75% of patients were able to return to employment(18). This improvement was sustained at 3 years follow up (19).

Following these promising results, the investigators now intend to undertake a fully powered RCT to confirm our hypothesis that 10kHz-SCS is beneficial for CNLBP patients with no prior back surgery.

To date 10kHz-SCS has not been formally tested against a sham control condition in order to isolate the therapeutic effects from those induced by placebo. It is very possible that some of the benefit reported may be due to a placebo effect (enhanced by a surgical procedure) or reporting bias in either the patient or assessor. The investigators have therefore specifically designed this fully powered double blind randomised sham controlled trial of 10kHz-SCS to address this major methodological limitation of previous studies.

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Samuel J Wesley; Phone Number: 07561062944; Email: samuel.wesley@gstt.nhs.uk
• Study Contact Backup: Name: Ramla A Abuukar Abdullahi; Phone Number: 83237 02071883237; Email: ramla.abuukarabdullahi@gstt.nhs.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Recruiting
    • Guy's and St Thomas Hospital
    • Principal Investigator: Adnan Al-Kaisy
    • Contact: Mays Jawad; Phone Number: 02071889811; Email: R&D@gstt.nhs.uk
  • Middlesbrough, United Kingdom, TS4 3BW
    • Not yet recruiting
    • South Tees Hospitals NHS Foundation Trust
    • Principal Investigator: Sam Eldabe, Md

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adults over the age of 18
2. Onset of low back pain > 12 months
3. Low back pain intensity > 60 out of 100mm on pain visual analogue scale (VAS)
4. Presence of clear component of neuropathic pain based on a PainDETECT Questionnaire score of >19 (we will monitor this inclusion criteria in the early stage of the trial and revise if necessary)
5. Degenerative disc disease confirmed by imaging or internal disc disruption as confirmed by discography
6. On stable pain medications, as determined by the Investigator, for at least 28 days prior to enrolling in this study and not change medication dosage without consulting Investigator
7. Legally able to provide informed consent
8. Able to comply with study-related requirements, procedures and visits

Exclusion Criteria:

1. Had previous spinal surgery
2. Chronic widespread pain
3. Subject has an active implanted device, whether turned on or off (e.g. pacemaker, intrathecal pump, deep brain stimulator etc.)
4. A current diagnosis of a progressive neurological disease such as multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, rapidly progressive arachnoiditis, rapidly progressive diabetic peripheral neuropathy, brain or spinal cord tumour, or severe/critical central or foraminal spinal stenosis
5. Mechanical spine instability detected by a clinician (validation by flexion/extension films of lumbar spine within the past 6 months showing 4 mm or more translational movement or excessive angular movement manifested by >5 degrees segmental angular movement) e.g. any forms of spondylolisthesis
6. A medical condition or pain in other area(s), not intended to be treated with SCS, that could interfere with study procedures, accurate pain reporting, and/or confound evaluation of study endpoints, as determined by the Investigator
7. Bleeding diathesis such as coagulopathy or thrombocytopenia
8. Immunocompromised and at an increased risk for infection
9. Systemic infection or local infection that would contraindicate SCS placement
10. Metastatic malignant disease or active local malignant disease
11. Pregnant (if female and sexually active, subject must be using a reliable form of contraception, be surgically sterile or be at least 2 years post-menopausal)
12. Active alcohol, marijuana, recreational or prescription drug abuse or dependence or unwilling to stop/reduce excessive inappropriate medication.
13. Evidence of an active disruptive psychological or psychiatric disorder or other known condition significant enough to impact perception of pain, compliance of intervention and/or ability to evaluate treatment outcome as determined by the Investigator
14. Concomitant participation in another clinical trial (surgery, device or drug)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Lead (AL); One octad lead placed where contacts 4 and 5 span the T9-T10 disc space.	Device: Nevro Senza System (HF10 Therapy); Nevro 10kHz High Frequency Spinal Cord Stimulation; Other Names: Neuromodulation; HF10; SCS; High-frequency stimulation; Nevro; HF-10; 10kHz SCS
Sham Comparator: Sham Lead (SL); One octad lead implanted subcutaneously behind the IPG and will serve to dissipate the current from the battery	Device: Nevro Senza System (HF10 Therapy); Nevro 10kHz High Frequency Spinal Cord Stimulation; Other Names: Neuromodulation; HF10; SCS; High-frequency stimulation; Nevro; HF-10; 10kHz SCS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean VAS Back Pain (7 Day Subject VAS Pain Diary)	Changes in mean VAS back pain between intervention and control at 6 months post-randomisation	6 months post randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oswestry disability index (v2.1a)	To compare disability between intervention and control at 1, 3, and 6 months post-randomisation.	1, 3, and 6 months post randomisation
PHQ-9 Questionnaire	To compare depression between intervention and control at 1, 3, and 6 months post-randomisation.	1, 3, and 6 months post randomisation
PSQI Questionnaire	To compare sleep quality between intervention and control at 1, 3, and 6 months post-randomisation.	1, 3, and 6 months post randomisation
PGIC Questionnaire	To compare patients' global impression of change between intervention and control at 1, 3, and 6 months post-randomisation.	1, 3, and 6 months post randomisation
EQ-5D Questionnaire	To compare health-related quality of life between intervention and control at 1, 3, and 6 months post-randomisation.	1, 3, and 6 months post randomisation
Medication Usage	To compare medication usage between intervention and control at 1, 3, and 6 months post-randomisation.	1, 3, and 6 months post randomisation
Sensation Map	To compare sensation maps between intervention and control at 1, 3, and 6 months post-randomisation.	1, 3, and 6 months post randomisation
Healthcare utilisation, work status, work absence, and out of pocket expenses	To compare the cost-effectiveness of 10kHz-SCS between intervention and control at six months post-randomisation.	6 months post randomisation
Safety/Adverse Events	To compare complications and adverse events at 6-months post-randomisation between intervention and control.	6 months post randomisation

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Collaborators: King's College London; University of Oxford; University of Liverpool; National Institute for Health Research, United Kingdom; University of Exeter; Pain And Neuromodulation Academic Research Centre (PANARC); James Cook University Hospital

Publications and helpful links

General Publications

• O'Connell NE, Ferraro MC, Gibson W, Rice AS, Vase L, Coyle D, Eccleston C. Implanted spinal neuromodulation interventions for chronic pain in adults. Cochrane Database Syst Rev. 2021 Dec 2;12(12):CD013756. doi: 10.1002/14651858.CD013756.pub2.
• Al-Kaisy A, Royds J, Palmisani S, Pang D, Wesley S, Taylor RS, Cook A, Eldabe S, McCracken L, Duarte R, Fairbank J. Multicentre, double-blind, randomised, sham-controlled trial of 10 khz high-frequency spinal cord stimulation for chronic neuropathic low back pain (MODULATE-LBP): a trial protocol. Trials. 2020 Jan 28;21(1):111. doi: 10.1186/s13063-019-3831-4.

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2018
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: March 13, 2018
• First Submitted That Met QC Criteria: March 13, 2018
• First Posted (Actual): March 20, 2018

Study Record Updates

• Last Update Posted (Actual): October 5, 2018
• Last Update Submitted That Met QC Criteria: October 3, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Neuromodulation; Spinal Cord Stimulation; SCS; HF10; HF-10; Nevro; High-frequency; 10kHz; CNLBP; Chronic Neuropathic Low Back Pain; Double blind randomised sham-controlled; PANARC
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Back Pain; Low Back Pain; Neuralgia; Pain, Intractable
• Other Study ID Numbers: Modulate-LBP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes