Frequency Modulated Neural Stimulation (FREMS) in Symptomatic Diabetic Neuropathy

NCT01628627 | Completed Phase 4

• 1 other identifier: EuropeanFREMS
• Study Type: interventional
• Target: 164
• Locations: 3 countries
• Sites: 6

Brief Summary

Aim of this study is to evaluate safety and efficacy of transcutaneous frequency modulated electromagnetic neural stimulation (FREMS) to treat symptomatic peripheral neuropathy in patients with diabetes mellitus.

Conditions

Diabetic Neuropathy, Painful

Keywords

Diabetic Neuropathy, Painful

Outcome Measures

Primary Outcomes (1)

• Change in Nerve Conduction Velocity of the Deep Peroneal, Tibial, or Sural Nerve

  Change in Nerve Conduction Velocity of the Deep Peroneal , Tibial, or Sural Nerve at 51 weeks (i.e., after three cycles of FREMS treatment) versus baseline

  baseline and 51 weeks

Secondary Outcomes (12)

• Change in Vibration Perception Threshold

  baseline and 51 weeks

• Change in Cold Sensory Threshold

  baseline and 51 weeks

• Change in Warm Sensory Threshold

  baseline and 51 weeks

• Change in Day Pain Intensity (Visual Analogue Scale)

  baseline and week 3

• Change in Day Pain Intensity (Visual Analogue Scale)

  week 17 and week 20

Study Arms (2)

FREMS

EXPERIMENTAL

Frequency Modulated Neural Stimulation (FREMS)

Device: Frequency Modulated Neural Stimulation (FREMS) (Aptiva)

Control

SHAM COMPARATOR

Device: sham treatment (Aptiva)

Interventions

Frequency Modulated Neural Stimulation (FREMS) (Aptiva) DEVICE

FREMS consisted of sequences of biphasic (negative and positive), asymmetric and electrically balanced pulses, composed of: 1) an active phase of high negative voltage spike (variable, max -300 V) and extra short duration (variable, 10-100 μsec, mostly \~40 μsec); followed by: 2) a recharging phase of low voltage and long duration (0.9 - 999 msec); pulse frequency was variable, ranging 1 to 1,000 Hz, mainly in the low range 1-50 Hz. Three cycles of 10 consecutive (one a day for 5 days/week) applications to both lower limbs were delivered.

Also known as: Aptiva device (Lorenz Biotech, Medolla, Italy)

FREMS

sham treatment (Aptiva) DEVICE

The sham treatment consisted of no electrical pulses delivered by the same device used to deliver the FREMS treatment and with the same treatment procedure and schedule.

Also known as: Aptiva device (Lorenz Biotech, Medolla, Italy)

Control

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 1 or Type 2 diabetes
• Diabetes duration of \> 1 year
• Age: 18 to 75 years
• Symptomatic neuropathy
• Abnormal amplitude, latency or conduction velocity in at least one motor nerve (Tibial or Peroneal) or in the Sural Nerve
• A measurable Sural Nerve conduction velocity
• Stable glycemic control in the last 3 months, HbA1C \< 11%
• MDNS score \> 7
• Stable dose of analgesic medications, if any, in the month prior enrollment

You may not qualify if:

• Previous treatment with TENS or other electrotherapy
• Motor or Sensitive nerve conduction velocity \< 30 non recordable/evocable
• Unstable glycemic control during last 3 months
• Pregnancy
• Implanted pacemaker or defibrillator or neurostimulator
• Cancer diagnosed in the last 5 years
• Psychological or psychiatric disorders that in the Investigator's opinion may interfere with patient's compliance to study procedures
• Active foot ulcer and/or major lower limb amputation
• Diabetic mononeuropathy
• Severe peripheral artery disease (Leriche Fontaine scale grade 3 and 4)
• Ankle-brachial index (ABI) \< 0.7
• Uremic neuropathy or end-stage renal disease
• Toxic neuropathies
• Severe hepatic disease
• Alcohol consumption ≥ 40 g/day or 30 units/week

Sponsors & Collaborators

• Lorenz Biotech S.p.A.: lead

Study Sites (6)

Paris-Nord University

Bondy, Ile Del France, France

Location

Heinrich Heine University

Düsseldorf, 40225, Germany

Location

San Raffaele Hospital & Scientific Institute

Milan, MI, 20132, Italy

Location

University of Padua

Padua, PD, 35143, Italy

Location

University of Perugia

Perugia, PG, 06100, Italy

Location

Tor Vergata University

Rome, RM, 00133, Italy

Location

Related Publications (3)

• Conti M, Peretti E, Cazzetta G, Galimberti G, Vermigli C, Pola R, Scionti L, Bosi E. Frequency-modulated electromagnetic neural stimulation enhances cutaneous microvascular flow in patients with diabetic neuropathy. J Diabetes Complications. 2009 Jan-Feb;23(1):46-8. doi: 10.1016/j.jdiacomp.2008.02.004. Epub 2008 Apr 10.

  PMID: 18403219 BACKGROUND

• Bosi E, Conti M, Vermigli C, Cazzetta G, Peretti E, Cordoni MC, Galimberti G, Scionti L. Effectiveness of frequency-modulated electromagnetic neural stimulation in the treatment of painful diabetic neuropathy. Diabetologia. 2005 May;48(5):817-23. doi: 10.1007/s00125-005-1734-2. Epub 2005 Apr 15.

  PMID: 15834546 BACKGROUND

• Bosi E, Bax G, Scionti L, Spallone V, Tesfaye S, Valensi P, Ziegler D; FREMS European Trial Study Group. Frequency-modulated electromagnetic neural stimulation (FREMS) as a treatment for symptomatic diabetic neuropathy: results from a double-blind, randomised, multicentre, long-term, placebo-controlled clinical trial. Diabetologia. 2013 Mar;56(3):467-75. doi: 10.1007/s00125-012-2795-7. Epub 2012 Dec 13.

  PMID: 23238789 DERIVED

MeSH Terms

Conditions

Diabetic Neuropathies

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Emanuele Bosi, MD

  San Raffaele Hospital & Scientific Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2012
• First Posted: June 27, 2012
• Study Start: May 1, 2006
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: June 27, 2012

Record last verified: 2012-06

Locations

IT (4); FR (1); DE (1)