New Grant Success
NIHR Grant success
The Utility Of Frequency-Modulated Electromagnetic Neural Stimulation (FREMS) As A Third Line Treatment In Patients With Painful Diabetes-Related Peripheral Neuropathy: A Randomised Controlled Trial (FREMS-PDPN)
NIHR have now accepted the final submission for funding with Dr Bernhard Frank as new chief Investigator
Scientific Abstract
Research question: Is Frequency Rhythmic Electrical Modulated System (FREMS) an effective treatment in patients with painful diabetic peripheral neuropathy (PDPN) and persistent pain despite trying at least two PDPN medications?
Background
PDPN affects 25% of people with diabetes and 70% of sufferers have moderate-to-severe pain. PDPN is associated with sleep disruption, poor quality of life (QoL), unemployment and depression. The average health care cost of PDPN in the UK is £2,511per patient per year, which increases with greater pain severity. The burden of PDPN is likely to increase with
increasing diabetes prevalence.
National Institute for Health and Care Excellence (NICE) guidance 173 recommended certain medications as initial treatments for PDPN. However, using these medications result in 50% reduction in pain in 33% of patients at best. These medications also have multiple significant side effects (such as weight gain, falls, urinary retention, constipation). Beyond these drugs, there are no NICE recommended treatments. As a result, many patients (43%) receive opioids, which have many unwanted side effects including addiction.
There is a clear need to identify a safe, well-tolerated, non-invasive, effective and cost- effective intervention in those who fail to respond to NICE recommended treatments. This could reduce medications and opioid use and improve QoL.
Aims and objectives
Efficacy objectives: 1. To evaluate the efficacy of FREMS using 11-point Likert numerical rating scale (NRS) 24-hour pain scores (0 to 10) averaged over the last 7 days (primary outcome). 2. Other outcomes: sleep, QoL and medication use amongst others. 3. To evaluate the cost effectiveness of FREMS in PDPN.
Safety objectives: To describe Adverse Events and Serious Adverse Events data (summarised both at patient level and event level).
Exploratory objectives: To investigate if patient phenotypes (demography, diabetes type, type of pain based on Neuropathic Pain Symptom Inventory [NPSI], mood, sleep) predict response to treatment.
Methods (please see flowchart in the uploads)
Design: A multi-centre 2-arm parallel group double blind RCT. The RCT will include an
internal pilot with stop/go criteria.
Setting: Patients will be recruited from 10 NHS Trusts that have PDPN services and the aligned primary care and podiatry services, as well as social media and Diabetes UK local patient groups. The study device will be placed in the hospital.
Population: Adults with PDPN for ≥3 months with significant pain (a mean total pain NRS ≥4 for the week before randomisation) despite trying at least 2 classes of medications.
Intervention: FREMS+ standard care
Comparator: TENS (Transcutaneous Electrical Nerve Stimulation )+ standard care Outcome: As above. The primary outcome is at 3 months and study end at 6 months.
Timelines: Protocol, database & CRFs: months 1-8; HRA, REC, MHRA approvals: 5-9; Site set-up: 8-13; Recruitment: 10-29; Follow-up: 13-35, Data Cleaning: 35-38; Analysis & dissemination: 36-41; Health economic analysis: 36-41; Final report: 41
Anticipated impact: The trial is designed to address gaps identified by NICE multiple technology appraisal (MTA) of FREMS in 2017. Hence the trial is likely to lead to a NICE TA
Dissemination: Via peer-reviewed articles, national/international presentations, Diabetes UK patients groups and social media. The investigators will liaise with the manufacturer & NICE. Study participants will be informed of the findings