FREMS-PDPN

FREMS-PDPN is a pragmatic, multi-centre, 2-arm, parallel group, double blind, sham controlled, randomised trial of patients with PDPN (defined as pain severity of ≥ 4 on 11-point numerical rating scale [NRS] measuring 24-hour pain scores [0 to 10] averaged over the last 7 days) who have not responded to at least two different classes of neuropathic pain medications as per NICE guidance.

FREMS-PDPN aims to recruit 356 adults with PDPN for ≥3 months with significant pain (mean pain Numerical Rating Scale [NRS] ≥4/10 for a week prior to randomisation) despite trying ≥2 different classes of PDPN medications.

Peripheral neuropathy is a common complication of diabetes and happens because of nerve damage in the feet and legs. Patients with neuropathy may have pain, discomfort or loss of feeling in the areas affected. The pain caused by peripheral neuropathy can badly affect sleep and quality of life. The standard treatment for nerve pain is medication but this doesn’t always work in some patients and there can also be side effects and problems tolerating the drugs.

FREMS-PDPN will test the clinical and cost-effectiveness of the frequency rhythmic electrical modulation system as a treatment for adults with Painful Diabetes-Related Peripheral Neuropathy (PDPN). We hope that FREMS treatment will reduce pain, and improve sleep quality and overall quality of life for patients living with PDPN.

Treatment and assessments are being conducted at NHS Trusts with PDPN services and aligned primary care and podiatry services. 

FREMS-PDPN is recruiting adult patients with diabetes who have experienced painful diabetic peripheral neuropathy in both feet for 3 months or more, or who have been taking pain medication for neuropathic pain for 3 months or more. Participants must have tried pain medication from at least two drug classes.

Participants will be randomised into one of two groups. They will either receive 10 treatments of the frequency rhythmic electrical modulation system (FREMS) or a sham treatment delivered using the same device but delivering high frequency transcutaneous electrical nerve stimulation (TENS). Participants in both groups will be allowed to continue with their standard care, as any changes in their use of pain medication will be recorded as a secondary outcome measure.

Primary Outcome

• 7-day average 24-hour pain on an 11-point NRS scale (0 = no pain and 10 = worst pain imaginable) measured at 3 months post-randomisation. 

Secondary Outcomes

Clinical

• 7-day average 24-hour pain on an 11-point NRS scale (0 = no pain and 10 = worst pain imaginable) measured at the end of treatment) and at 6 months
• Neuropathic Pain Impact on Quality-of-Life Questionnaire (NePIQoL) as a measure of disease specific quality of life at 3 and 6 months
• Treatment success (measured as a 30% reduction in 7-day average 24-hour pain scores) at end of treatment, 3 months and 6 months
• Treatment success (measured as a 50% reduction in 7-day average 24-hour pain scores) at end of treatment, 3 months and 6 months.
• Area Under the Curve (AUC) for the daily NRS pain scores over the study period (from baseline to 3 months and from baseline to 6 months)
• Brief Pain Inventory-Diabetic Peripheral Neuropathy (BPI-DPN) as a measure of pain interference with function total score at 3 and 6 months
• Beck Depression Inventory as a measure of depression at 3 and 6 months
• Pittsburgh Sleep Quality Index (PSQI) as a general measure of sleep quality at 3 and 6 months
• Patient and Clinician Global Impression of Change at end of treatment, 3 months and 6 months
• Changes to pain medications (frequencies and dosages) at 3 and 6 months
• Patient perception of their treatment arm at the end of the treatment phase

Cost-Effectiveness

• Health-related QoL at 6 months assessed by the EuroQoL-5D-5L
• Health resource use at 3 and 6 months
• Cost per quality adjusted life year (QALY) gained over 6 months.

FREMS-PDPN is sponsored by the University of Birmingham. It is being coordinated by Birmingham Clinical Trials Unit and is funded by the government through the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (ref: NIHR133599). The chief investigator for the trial is Dr Bernhard Frank, based at The Walton Centre NHS Foundation Trust, Liverpool.