Frequency Modulated Neural Stimulation (FREMS) in Symptomatic Diabetic Neuropathy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Lorenz Biotech S.p.A.
ClinicalTrials.gov Identifier:
NCT01628627
First received: June 23, 2012
Last updated: June 26, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Diabetic Neuropathy, Painful
Device: Frequency Modulated Neural Stimulation (FREMS) (Aptiva)
Device: sham treatment (Aptiva)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Long Term, Double Blind, Randomized, Placebo Controlled Multi-center Study of FRE.M.S.- Frequency Modulated Neural Stimulation Lorenz Therapy™ in Symptomatic Diabetic Neuropathy

Resource links provided by NLM:


Further study details as provided by Lorenz Biotech S.p.A.:

Primary Outcome Measures:
  • Change in Nerve Conduction Velocity of the Deep Peroneal, Tibial, or Sural Nerve [ Time Frame: baseline and 51 weeks ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Change in Vibration Perception Threshold [ Time Frame: baseline and 51 weeks ] [ Designated as safety issue: No ]
    Change in Vibration Perception Threshold at 51 weeks (i.e., after three cycles of FREMS treatment) versus baseline

  • Change in Cold Sensory Threshold [ Time Frame: baseline and 51 weeks ] [ Designated as safety issue: No ]
    Change in Cold Sensory Threshold at 51 weeks (i.e., after three cycles of FREMS treatment) versus baseline

  • Change in Warm Sensory Threshold [ Time Frame: baseline and 51 weeks ] [ Designated as safety issue: No ]
    Change in Warm Sensory Threshold at 51 weeks (i.e., after three cycles of FREMS treatment) versus baseline

  • Change in Day Pain Intensity (Visual Analogue Scale) [ Time Frame: baseline and week 3 ] [ Designated as safety issue: No ]
    Change in Pain Intensity (assessed using Visual Analogue Scale) during day time with the first cycle of FREMS

  • Change in Day Pain Intensity (Visual Analogue Scale) [ Time Frame: week 17 and week 20 ] [ Designated as safety issue: No ]
    Change in Pain Intensity (assessed using Visual Analogue Scale) during day time with the second cycle of FREMS

  • Change in Day Pain Intensity (Visual Analogue Scale) [ Time Frame: week 34 and week 37 ] [ Designated as safety issue: No ]
    Change in Pain Intensity (assessed using Visual Analogue Scale) during day time with the third cycle of FREMS

  • Change in Night Pain Intensity (Visual Analogue Scale) [ Time Frame: baseline and week 3 ] [ Designated as safety issue: No ]
    Change in Pain Intensity (assessed using Visual Analogue Scale) during night time with the first cycle of FREMS

  • Change in Night Pain Intensity (Visual Analogue Scale) [ Time Frame: week 17 and week 20 ] [ Designated as safety issue: No ]
    Change in Pain Intensity (assessed using Visual Analogue Scale) during night time with the second cycle of FREMS

  • Change in Night Pain Intensity (Visual Analogue Scale) [ Time Frame: week 34 and week 37 ] [ Designated as safety issue: No ]
    Change in Pain Intensity (assessed using Visual Analogue Scale) during night time with the third cycle of FREMS

  • Change in the Michigan Diabetic Neuropathy Score (MDNS) [ Time Frame: baseline and 51 weeks ] [ Designated as safety issue: No ]
    Change in the Michigan Diabetic Neuropathy Score (MDNS) at 51 weeks (i.e. after three FREMS cycles) versus baseline

  • Change in the dose and type of analgesic medications [ Time Frame: baseline and 51 weeks ] [ Designated as safety issue: No ]
    Change in the dose and type of analgesic medications at week 51 (i.e. after three FREMS cycles) versus baseline

  • Number of patients with treatment-related adverse events [ Time Frame: baseline and 51 weeks ] [ Designated as safety issue: No ]
    Change in the dose and type of analgesic medications at week 51 (i.e. after three FREMS cycles) versus baseline


Enrollment: 164
Study Start Date: May 2006
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FREMS
Frequency Modulated Neural Stimulation (FREMS)
Device: Frequency Modulated Neural Stimulation (FREMS) (Aptiva)
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.
Other Name: Aptiva device (Lorenz Biotech, Medolla, Italy)
Sham Comparator: Control Device: sham treatment (Aptiva)
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.
Other Name: Aptiva device (Lorenz Biotech, Medolla, Italy)

Detailed Description:

Diabetic neuropathy is a common and potentially disabling complication of patients with type 1 or type 2 diabetes due to the damage of peripheral nerves caused by chronic hyperglycemia. The most common clinical signs and symptoms of diabetic neuropathy include numbness, diminished sensation and painful symptoms, such as burning, pins and needles, intolerable pain and hyperaesthesia of the lower extremities.

Different classes of drugs, such as analgesics, antidepressants and anti-epileptics are variably efficacious in pain relief, but are unfortunately unable to revert the natural history of the disease.

A wide range of electrotherapies have been proposed for the non-pharmacological treatment of diabetic neuropathy. The rationale of using electric or magnetic stimulation is the potential enhancement of microcirculation and endoneural blood flow, possibly counteracting the nerve ischemic damage, together with other yet poorly understood mechanisms, such as masking pain by interfering with pain gate control.

A number of studies have reported the efficacy of different electrotherapies, such as transcutaneous electrical nerve stimulation (TENS), pulsed-dose electrical stimulation, peripheral nerve, nerve root, spinal cord, deep brain and epidural motor cortex stimulations, pulsed (electro-)magnetic fields and static magnetic fields, high-frequency external muscle stimulation, high-tone external muscle stimulation and external muscle stimulation. However, of all these electrotherapies, only TENS is currently recommended as a treatment for painful diabetic neuropathy by the American Academy of Neurology.

Recently, a novel transcutaneous frequency-modulated electromagnetic neural stimulation (also named as Frequency Rhythmic Electrical Modulation System, FREMS), has been developed. FREMS consists of a sequence of modulated electrical stimuli that varies automatically in terms of pulse frequency, duration and voltage amplitude. FREMS was tested in a pilot randomized, cross-over study, and reduced diabetic neuropathy pain and ameliorated the sensory tactile and vibration perception threshold and motor nerve conduction velocity compared to a sham treatment.

The aim of this study was to test the efficacy and safety of FREMS in a multicentre, randomized, double-blind, placebo-controlled study enrolling a large population with symptomatic diabetic polyneuropathy, with repeated treatment sessions and a post-treatment follow-up of adequate length.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01628627

Locations
France
Paris-Nord University
Bondy, Ile del France, France
Germany
Heinrich Heine University
Düsseldorf, Germany, 40225
Italy
San Raffaele Hospital & Scientific Institute
Milano, MI, Italy, 20132
University of Padua
Padua, PD, Italy, 35143
University of Perugia
Perugia, PG, Italy, 06100
Tor Vergata University
Rome, RM, Italy, 00133
Sponsors and Collaborators
Lorenz Biotech S.p.A.
Investigators
Principal Investigator: Emanuele Bosi, MD San Raffaele Hospital & Scientific Institute
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Lorenz Biotech S.p.A.
ClinicalTrials.gov Identifier: NCT01628627     History of Changes
Other Study ID Numbers: EuropeanFREMS
Study First Received: June 23, 2012
Last Updated: June 26, 2012
Health Authority: Italy: Ministry of Health

Keywords provided by Lorenz Biotech S.p.A.:
Diabetic Neuropathy, Painful

Additional relevant MeSH terms:
Diabetic Neuropathies
Peripheral Nervous System Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Nervous System Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on October 20, 2014