Condition category
Nervous System Diseases
Date applied
06/11/2019
Date assigned
01/01/2020
Last edited
18/11/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Radicular pain (RP) is the most common cause of nerve-related pain in the lower back and legs. It may become a chronic pain (lasting more than 3 months) in 30% of cases. The most frequent cause of radicular pain is disc herniation in patients less than 50 years old, and degenerative spinal disease in the over 50’s.

Significant pain relief may be achieved with an injection of a local anaesthetic around the nerves where they exit the spinal column (dorsal root ganglion [DRG]). Additionally, PRF therapy plays a crucial role in the treatment of RP. Studies also report a 100% safety record with PRF with no adverse neurological outcomes.

The aim is to investigate the cellular components (of both blood and spinal fluid) of patients with lower back and leg pain. We will compare the blood and spinal fluid samples both before and after a pain treatment called pulsed radiofrequency

Who can participate?
Patients aged between 18-60 years with chronic low back and leg pain in a definite nerve distribution and a bulging disc present on an MRI scan (which corresponds to the distribution of pain)

What does the study involve?
After consenting, a sample of cerebrospinal fluid (CSF) and a peripheral blood sample will be taken. A PRF procedure will be performed (or simply local anaesthetic if in control group) At standard points post treatment, the patients will be re-assessed

What are the possible benefits and risks of participating?
Inclusion in this study offers no benefits other than to progress the understanding of cause of chronic nerve pain and help us to decide whether we should give all patients PRF treatment or not.
There is a risk of infection, bleeding, nerve damage and headache (1 in 200) related to pain procedure and spinal fluid sampling

Where is the study run from?
Hermitage Medical Clinic, Ireland

When is the study starting and how long is it expected to run for?
January 2020 to December 2020

Who is funding the study?
Investigator initiated and funded

Who is the main contact?
Dr Deborah Galvin
deborahgalvin@yahoo.ie

Trial website

Contact information

Type

Scientific

Primary contact

Dr Deborah Galvin

ORCID ID

http://orcid.org/0000-0002-3506-195X

Contact details

Trinity Translational Medicine Institute
Trinity Centre for Health Sciences Trinity College Dublin
St James’s Hospital
Dublin
8
Ireland
+353 1 896 3268
deborahgalvin@yahoo.ie

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

Nil known

Study information

Scientific title

An investigation of the effect of Pulsed Radiofrequency treatment of the Dorsal Root Ganglion on cerebrospinal fluid and peripheral venous blood cellular, proteomic and neuropeptide concentrations with clinical outcome correlation in patients with chronic lumbosacral radicular pain

Acronym

Study hypothesis

We aim to:
1. Identify and quantify changes in the number of neuroimmune cells (CD4+ T cell, CD8+ T cell) and natural killer cells in cerebrospinal fluid and peripheral venous blood samples before and after pulsed radiofrequency therapy in patients with radicular pain
2. Identify changes in neuropeptides and cytokines implicated in neuropathic pain conditions following PRF (BDNF, Substance P, NGF, MCP-1, VEGF, IFN-gamma, IL-1, IL-6, TNF, PDL-1)
3. Characterise the proteome in CSF and VB in patients with RP and the effect of PRF therapy on the proteome
4. Quantify the clinical effect of PRF

Ethics approval

Approved 07/10/2019, Hermitage Medical Clinic Ethics Committee (Old Lucan Road, Dublin, D20 W722, Ireland; +353 1 6459000; ethics@hermitageclinic.ie), ref: none provided

Study design

Single-center randomized triple-blinded controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Chronic, radicular, lumbosacral pain

Intervention

Patients will be randomised to receive a single session of pulsed radiofrequency therapy (PRF) or a sham procedure.

PRF is a treatment for chronic pain which occurs in the path of a particular nerve(s). A radiofrequency probe with an active tip is placed under fluoroscopic guidance. A small amount of radio-opaque dye is used to identify the nerve root to the epidural space (dorsal root ganglion, DRG).When probe appears in a satisfactory position, sensory stimulation (50 Hz) is sought at an output of less than 0.4 Volts. The probe is manipulated until the patient reports paraesthesia in a distribution concordant with the usual painful distribution. If the paraesthesia is not elicited in the correct dermatome, another probe will be placed at a neighbouring DRG to map the paraesthesia to the usual pain distribution. Once this is achieved, motor stimulation (2 Hz) at greater than 1.5 times the sensory stimulation is checked. Impedence less than 450 Ohms is required. One ml of lidocaine 1% is applied to the DRG.

The treatment group (LA + PRF) receive one pulsed radiofrequency treatment to the DRG - at less than 420C for 120 seconds with pulses (20 milliseconds at 500,000 Hz) at 2 Hz and a voltage output of 45 Volts.

The patients in the control group (LA) receives 120 seconds free of stimulation.

Follow-up:
Assessments will be made at the following time points:
- Immediately before the procedure (T0)
- 1 hour after the procedure (Global Perceived Effect and Numerical Rating Scale only) (T1)
- 1 month post procedure (T2)
- 3 months post procedure (T3)
- 6 months post procedure (T4)


Randomisation process: Randomisation will be performed in Trinity Translational Medicine Institute. They will use a computerised, random number generator and use block allocations (block sizes of 2 and 4). Patients will be randomised and the RF machine operator (theatre nurse) will be given a sealed envelope to open with the treatment direction when the RF probe is sited. The machine operator will return the form with patient ID and treatment details in a sealed envelope. If the DRG block procedure fails, regardless of whether the patient receives PRF or not, details of the failed block will be included on the randomisation sheet and the patient will be excluded from the study, and another patient will be re-allocated to this group.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

The concentration of CD4+ T cells measured in the CSF at 3 months (T3) post PRF

Secondary outcome measures

Measured using cerebrospinal fluid and peripheral venous blood samples:
1. NK cell and CD8+ T cell numbers at baseline and T3
2. CD4+/CD8+ ratio at baseline and T3
3. CSF neuropeptide and cytokine concentrations at baseline and T3

Secondary outcomes (clinical):
4. Improvement in symptoms (on the Global Perceived Effect (GPE) - Likert Scale) at baseline and T3
5. Pain score (Numerical Rating Scale [NRS]) at baseline and T3
6. Global Perceived Effect (GPE) on Likert Scale and NRS at one hour (T1), one month (T2), and 6 months (T4) post PRF.
7. Quality of Life measured using the RAND-36 at T2, T3 and T4
8. Functional ability measured using the Oswestry Disability Index at T2, T3 and T4
9. Medication usage measured using the Medication Quantification Scale III at T2, T3 and T4
10. Adverse events at T1, T2, T3 and T4
11. Further interventions required at T2, T3 and T4

Overall trial start date

08/07/2019

Overall trial end date

21/12/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Age range 18-60 years
2. Unilateral monosegmental radicular pain in the lumbosacral nerve roots
3. Symptoms consistent with MRI findings of a contained herniated disc
4. Chronic pain lasting more than 3 months
5. Failed conservative medical management for over one month (medication and physical therapy)
6. Radicular pain is the primary complaint with minimal axial pain
7. NRS of > 3 (on 11-point NRS)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

10

Participant exclusion criteria

1. Patient refusal
2. Atypical or bilateral radicular pain patterns
3. Axial pain
4. Cognitive impairment or language barriers that could impair the patients understanding and reporting of outcomes
5. Malignancy
6. Vertebral fractures
7. Multiple sclerosis
8. Connective tissue diseases
9. Infection
10. Pregnancy or breast-feeding
11. Prior Spinal surgery
12. Lumbar spine interventions in the last 6 months (epidural injections or PRF)
13. Coagulation disorder or anti-coagulant treatment
14. Psychiatric disorder
15. Allergy to local anesthetics or contrast medium
16. Dependent Personnel such as staff members, students or NCHDs
17. Pre-operative NSAID, corticosteroid, methotrexate, monoclonal antibody therapy or opioid therapy
18. Patients will be excluded from the study if appropriate nerve stimulation during the PRF procedure or pain relief (more than 50%) post DRG block are not achieved

Recruitment start date

22/01/2020

Recruitment end date

21/12/2020

Locations

Countries of recruitment

Ireland

Trial participating centre

Hermitage Medical Clinic
Old Lucan Road
Dublin
D20 W722
Ireland

Sponsor information

Organisation

Trinity Translational Medicine Institute

Sponsor details

Trinity Centre for Health Sciences Trinity College Dublin
St James’s Hospital
Dublin 8
8
Ireland
+353 1 896 3268
deborahgalvin@yahoo.ie

Sponsor type

Research organisation

Website

Funders

Funder type

Other

Funder name

Investigator initiated and funded

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Neuroimmunology journal
Chronic pain journal

IPD sharing statement:
The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository. Only the three authors will have access to the data. Once journal publication has been achieved the data will be irreversibly deleted. Patients will be identified by code. Data will be stored for 5 years.

Intention to publish date

01/06/2021

Participant level data

Stored in repository

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

18/11/2019: Trial’s existence confirmed by Hermitage medical clinic