Clinical and technical evidence

Advice

Published evidence
Overall assessment of the evidence
Recent and ongoing studies

Clinical and technical evidence

A literature search was carried out for this briefing in accordance with the interim process and methods statement. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting mibs@nice.org.uk.

Published evidence

Four studies are summarised in this briefing with a total of 151 participants. Two of these studies are randomised double-blind crossover studies, 1 is a randomised controlled trial and 1 is a case/control study. All studies were conducted in Europe.

Table 3 summarises the clinical evidence and its strengths and limitations.

Overall assessment of the evidence

The evidence base is very limited in quality and quantity. Two studies used the same sample but reported different outcomes. Three studies had small sample sizes which could affect the reliability of the results. None of the studies used a comparator device, 3 used a placebo or sham condition as their comparator and 1 had no comparator. Two studies used the predecessor device, the PhysioFlog ETS 501. Because the devices are functionally similar, the results seem likely to be generalisable to the Aptiva device. All of the studies showed benefits of using the Aptiva device, including reduced pain and improved quality of life.

Although the studies included were not conducted in the UK, the outcomes reported are relevant to the NHS care pathway. It would be beneficial to have evidence directly comparing Aptiva with current NHS treatment options, including evidence from patients in whom treatment has failed. Longer follow-up periods would also show if the Aptiva device provides sustained benefits to patients.

Table 3 Summary of selected studies

Bocchi et al. (2010)
Study size, design and location	10 adult healthy controls and 10 adult patients with type 2 diabetes and diagnosed polyneuropathy. Case–control design. Italy.
Intervention and comparator(s)	Aptiva FREMS; no comparator.
Key outcomes	Blood flow improved in both groups after FREMS treatment. Mean difference in blood flow in healthy participants was 10% higher compared to those with diabetes after treatment. During treatment, there was a statistically significant increase in vasomotion power spectra in the diabetes group only. There was a non-significant increase in the healthy control group. After treatment, relative energy values around the 0.1 Hz peak of the power spectra remained significantly higher in the diabetes group.
Strengths and limitations	Within-patient control design. Small sample sizes. No comparator. Vasomotion power spectra results may not be a relevant clinical outcome.
Bosi et al. (2005)
Study size, design and location	31 adult patients with type 1 or type 2 diabetes and painful neuropathy. Randomised, double-blind crossover design. Italy.
Intervention and comparator(s)	PhysioFlog ETS 501 FREMS and placebo (sham treatment using the same device with no electrical stimulation) in 2 cycles of 10 treatments with each intervention in random sequence, with each series lasting no more than 3 weeks.
Key outcomes	After FREMS treatment there was a significant decrease in daytime and night-time pain scores and a significant increase in vibration perception across all recruited patients. Motor nerve conduction velocity and sensitivity to the Semmes-Weinstein monofilament pressure test were recorded for 26 and 12 patients respectively and a significant increase was observed after FREMS therapy in those tested. These improvements persisted up to the final follow-up at 4 months. No significant differences were observed after placebo treatment. At 4-month follow-up, there were significant improvements in quality of life (SF-36).
Strengths and limitations	Randomised double-blind design. Funded in part by a research grant from Lorenz Biotech (the original manufacturer).
Bosi et al. (2013)
Study size, design and location	110 adult patients with a diagnosis of type 1 or 2 diabetes with symptomatic neuropathy. Randomised controlled trial. Six sites across Italy, Germany and France.
Intervention and comparator(s)	Aptiva FREMS and placebo (sham treatment using the same device with no electrical stimulation).
Key outcomes	There was no significant difference in the change in nerve conductance velocity (NCV) between groups. Night-time and daytime pain was significantly reduced in the intervention group up to 37 weeks after initial treatment. Total follow-up was 51 weeks. The difference in pain between groups was not significant 3 months after the last treatment. There was no significant difference in the change in tactile sensation between groups. There was a significant increase in cold sensation threshold in the intervention group compared with the placebo group.
Strengths and limitations	Long follow-up. Randomised double-blind design. Large sample size. Focused on mild neuropathy only. Funded by Lorenz Lifetech. Patients were already medicated at baseline.
Conti et al (2009)
Study size, design and location	Same sample used by Bosi et al. (2005). Randomised, double-blind crossover design. Italy.
Intervention and comparator(s)	PhysioFlog ETS 501 FREMS and placebo (sham treatment using the same device with no electrical stimulation).
Key outcomes	Within the 3-week treatment timeframe, there were no changes in skin cutaneous blood flow after FREMS or placebo treatment. TcPO₂ appeared significantly reduced after FREMS treatment during rest. There were no significant changes in TcPCO₂. At 4-month follow-up, there was a significant increase in cutaneous blood flow during rest compared with baseline.
Strengths and limitations	Funded in part by a research grant from Lorenz Biotech. Randomised double-blind design.
Abbreviations: VEGF, vascular endothelial growth factor; FREMS, frequency modulated electromagnetic neural stimulation; NCV, nerve conductance velocity; SF-36, short form-36 questionnaire; TcPO₂, transcutaneous oxygen pressure; TcPCO₂,_{transcutaneous carbon dioxide pressure.}

Recent and ongoing studies

No ongoing or in-development trials were identified.