AzTrials
AzTrials

Diabetic Neuropathy, PainfulPhase 4NCT01628627

Frequency Modulated Neural Stimulation (FREMS) in Symptomatic Diabetic Neuropathy

A Phase 4 study testing Frequency Modulated Neural Stimulation (FREMS) (Aptiva) in people with Diabetic Neuropathy, Painful, run by Lorenz Biotech S.p.A. at 6 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Diabetic Neuropathy, Painful
What is being tested?
Frequency Modulated Neural Stimulation (FREMS) (Aptiva)
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
164 participants
Where
6 sitesin 3 countries
Study dates
May 2006to Apr 2010
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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

Trial locations and contacts

6 sites in 3 countries.

6 sites in 3 countries

Italy4 sites

  • San Raffaele Hospital & Scientific Institute

    Milan, MI, 20132

  • University of Padua

    Padua, PD, 35143

  • University of Perugia

    Perugia, PG, 06100

  • Tor Vergata University

    Rome, RM, 00133

Other trials in Italy

France1 site

  • Paris-Nord University

    Bondy, Ile Del France

Other trials in France

Germany1 site

  • Heinrich Heine University

    Düsseldorf, 40225

Other trials in Germany

About this study

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

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.

Read the 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.

Being tested
Frequency Modulated Neural Stimulation (FREMS) (Aptiva), sham treatment (Aptiva)
Keywords
Diabetic Neuropathy, Painful
Medical subject headings
Diabetic Neuropathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Also called Aptiva device (Lorenz Biotech, Medolla, Italy)

    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.

  • sham treatment (Aptiva)Device

    Also called Aptiva device (Lorenz Biotech, Medolla, Italy)

    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.

Study groups in NCT01628627
Study groupRoleWhat they receive
FREMSExperimentalFrequency Modulated Neural Stimulation (FREMS)
Receives: Device: Frequency Modulated Neural Stimulation (FREMS) (Aptiva)
ControlSham comparatorNot described
Receives: Device: sham treatment (Aptiva)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: baseline and 51 weeks

Secondary outcomes (12)

  1. Change in Vibration Perception Threshold

    Change in Vibration Perception Threshold at 51 weeks (i.e., after three cycles of FREMS treatment) versus baseline

    Measured: baseline and 51 weeks

  2. Change in Cold Sensory Threshold

    Change in Cold Sensory Threshold at 51 weeks (i.e., after three cycles of FREMS treatment) versus baseline

    Measured: baseline and 51 weeks

  3. Change in Warm Sensory Threshold

    Change in Warm Sensory Threshold at 51 weeks (i.e., after three cycles of FREMS treatment) versus baseline

    Measured: baseline and 51 weeks

  4. Change in Day Pain Intensity (Visual Analogue Scale)

    Change in Pain Intensity (assessed using Visual Analogue Scale) during day time with the first cycle of FREMS

    Measured: baseline and week 3

  5. Change in Day Pain Intensity (Visual Analogue Scale)

    Change in Pain Intensity (assessed using Visual Analogue Scale) during day time with the second cycle of FREMS

    Measured: week 17 and week 20

  6. Change in Day Pain Intensity (Visual Analogue Scale)

    Change in Pain Intensity (assessed using Visual Analogue Scale) during day time with the third cycle of FREMS

    Measured: week 34 and week 37

  7. Change in Night Pain Intensity (Visual Analogue Scale)

    Change in Pain Intensity (assessed using Visual Analogue Scale) during night time with the first cycle of FREMS

    Measured: baseline and week 3

  8. Change in Night Pain Intensity (Visual Analogue Scale)

    Change in Pain Intensity (assessed using Visual Analogue Scale) during night time with the second cycle of FREMS

    Measured: week 17 and week 20

  9. Change in Night Pain Intensity (Visual Analogue Scale)

    Change in Pain Intensity (assessed using Visual Analogue Scale) during night time with the third cycle of FREMS

    Measured: week 34 and week 37

  10. Change in the Michigan Diabetic Neuropathy Score (MDNS)

    Change in the Michigan Diabetic Neuropathy Score (MDNS) at 51 weeks (i.e. after three FREMS cycles) versus baseline

    Measured: baseline and 51 weeks

  11. Change in the dose and type of analgesic medications

    Change in the dose and type of analgesic medications at week 51 (i.e. after three FREMS cycles) versus baseline

    Measured: baseline and 51 weeks

  12. Number of patients with treatment-related adverse events

    Change in the dose and type of analgesic medications at week 51 (i.e. after three FREMS cycles) versus baseline

    Measured: baseline and 51 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jun 2012 (estimated)
  2. Study startMay 2006
  3. Primary completionApr 2010
  4. Study completionApr 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
164 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01628627
Sponsor's protocol ID
EuropeanFREMS
Status last verified
Jun 2012
First submitted
23 Jun 2012
Last updated
27 Jun 2012
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 18403219

  • 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.

    PubMed 15834546

  • 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.

    PubMed 23238789

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Frequency Modulated Neural Stimulation (FREMS) (Aptiva) in people with Diabetic Neuropathy, Painful, run by Lorenz Biotech S.p.A. at 6 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Italy, France, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Nerve Conduction Velocity of the Deep Peroneal, Tibial, or Sural Nerve (time frame: baseline and 51 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01628627, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2012.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in