Leprosy Neuropathy Clinical Trial
Official title:
Evaluation of Low Level Laser Therapy Effects in Peripheral Nerves Patient Affected With Leprosy : Randomized Controlled Trial
We are going to investigate leprosy patients with neuropathies. This problem can lead to changes in nerve function and lead to disability. We will investigate a protocol with LLLT to improve pain, inflammation, and to prevent disabilities. We will test two groups, which will be divided into control and LLLT treated patients. In this groups we will perform quantitative measurements of the following parameters before and after the protocol application: electroneuromyography and muscle strength measurements, evaluation of activity limitation and risk awareness, evaluation of tactile sensitivity and evaluation of temperatures of hands and feet. Averages for all parameters will be compared before and after treatment (12 application sessions). We believe that LLLT can become an important alternative treatment to improve conduction velocity, tactile sensitivity, temperatures of hands and feet, muscle strength and pain, which will prevent nerve damage and disabilities
Leprosy is an infectious disease caused by Mycobacterium leprae, which is an obligate
intracellular bacillus with the capacity to invade cells of the peripheral nervous system
(Nations et al., 1998). This disease presents polymorphic clinical features, and the
destruction of peripheral nerves is relevant, resulting in irreversible disabilities with
great social and psychological impact (Martins et al., 2008).
Among the 250,000 new cases of leprosy detected worldwide every year, 12% to 55% demonstrate
diagnosis of sensory, motor or autonomic neuropathy (Saunderson et al., 2000). The
destruction of nerve fibers in patients with leprosy can be established by the presence of
inflammatory process and the development of autoimmunity and cytotoxicity (Birdi et al.,
1996), including nerve growth factor (Facer et al., 1998), glia cells' adhesion molecules,
interferon-gamma,Transforming Growth Factor - Beta (Goulart et al., 1996; Goulart et al.,
2000), Tumor Necroses Factor-alpha (Singh, 1998) and interleukins (IL-6, IL-8, IL-12 and
IL-10) (Mendonça et al., 2008).
Low Level Laser Therapy (LLLT) has been demonstrated as a promising treatment in neural
rehabilitation. Some studies, has demonstrated that LLLT presented positive results in
improving nerve conduction velocity. The literature has provided evidences for the
effectiveness of LLLT treatment in neural rehabilitation, and it may be a promising tool for
leprosy neuropathies rehabilitation.
LLLT provided improvements in clinical and electrophysiological parameters in humans with
ulnar neuropathy and this modality showed a satisfying short-term effectiveness in the
treatment of this pathology (Ozkan et al., 2014). Other studies have shown that the LLLT
application in diabetic polyneuropathy presented positive results in improving nerve
conduction velocity (Khamseh et al., 2011).
Such neuropathies are associated with significant physical disabilities, generating high
social-economic cost, an important challenge for clinical interventions. Currently, leprosy
neuropathies are treated with standard protocols, using either corticoid treatment regimens
and/or surgical interventions for nerve decompression. Therefore, LLLT may be a novel
auxiliary therapeutic resource in leprosy in order to improve patients' nerve conduction
velocity, diminish pain, and minimize physical disabilities, probably reducing the usage
period of maximum dose of corticoids, and the number of surgical procedures in the future.
Furthermore, this therapeutic approach is also a non-invasive treatment and has a relatively
low cost.
Despite the absence of studies on LLLT effects in affected nerves of patients with leprosy,
there are some studies showing positive effects in other neuropathies, such as: improvement
in clinical and electrophysiological parameters, reduction of pain, improvement of
inflammation in nerve entrapment neuropathy, as well as for the promotion of nerve
regeneration. Considering that LLLT approach may promote analgesic effects (Chen et al.,
2014; Ozkan et al., 2014), improve clinical and electrophysiological parameters (Ozkan et
al., 2014; Khamseh et al., 2011), induce anti-inflammatory effects and nerve repair (Chen et
al., 2014; Lazovic et al., 2014; Alcântara et al., 2013; Hsieh et al., 2012), and reduce
degeneration of the myelin sheat by increasing conduction velocity (Khamseh et al., 2011) in
other neuropathologies, we believe that LLLT may also promote the favourable effects in
leprosy neuropathy.
This work aims to evaluate the effects of the application of LLLT in the peripheral nerve of
leprosy patients. This project was approved N. 989.148/2015 by the Research Ethics Committee
of the Federal University of Uberlandia. A randomized, double-blind, placebo-controlled
clinical trial will be conducted from January 2017 to December 2019.
The patients will be recruited at the National Reference Centre for Sanitary Dermatology and
Leprosy (CREDESH), Federal University of Uberlandia (UFU), State of Minas Gerais, Brazil and
then will be informed about the study procedures and will sign the informed consent form.
CREDESH is a public health care facility in an endemic region where routine prevention,
including intradermal Bacilo Calmette-Guérin (BCG) vaccination, Household Contacts (HHCs)
monitoring, early case detection and treatment are available and are under supervision, with
multidisciplinary team.
Adult patients (n=92) aged 18-60 years old diagnosed with presence of focal demyelinating
neuropathy in compression sites of the ulnar and common peroneal nerves. The patients are
selected of household contacts group who became ill during the follow up for 5 to 7 years in
the epidemiological surveillance program of the CREDESH/UFU. Clinical dermato-neurological
examination, serology anti-PGL-1 are performed annually. When participants present more than
one positive result during follow-up, they will undergo in six slit-skin smear sampling for
bacilloscopy and quantitative PCR (qPCR) M. leprae DNA with M. leprae-specific repetitive
element (RLEP3) detection (lobes of the right and left ears; right and left elbow and right
and left knee). Then, the patients are forwarded for dermato-neurological examination,
sensitivity and muscle force evaluation (hands, feet and eyes), incapacity degree
evaluation, electroneuromyography examination of upper and lower limb. All patients will be
treated with multidrug therapy (MDT), according to their operational classification
(Paucibacillary - PB and Multibacillary - MB) and their Ridley Jopling classification
(tuberculoid and/or borderline tuberculoid (TT), borderline-borderline (BB), borderline
lepromatous (BL) and lepromatous (LL)). The patients will be randomized and divided into two
groups:
1. Control: patients who will receive application "sham LLLT". The laser will be turned
off, but the procedure will be the same as with the LLLT group);
2. LLLT: patients who will receive treatment with LLLT for 12 sessions in alternate days
during 4 weeks on nerves:
1. ulnar nerve: laser probe will be applied around the ulnar nerve at the elbow
region, especially in the region of the cubital tunnel at a total of 5 points (3
points above and two points below at medial epicondyle. The distance between of
the applications points is 1cm.
2. common peroneal nerve: will be applied LLLT at 2 points above and 3 points
surrounding fibular head. The distance between of the applications points is 1cm.
The LLLT will be applied using a diode laser device with parameters: 830
nanometers (nm), 100 milliwatts (mW), 8 Joules (J), 3mW/cm2. Laser probe will be
applied directly and perpendicularly in skin contact, the time of irradiation will
be 80 seconds per point and treatments will be applied for three times a week for
12 sessions.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Active, not recruiting |
NCT03324035 -
Treatment of Neuropathic Pain in Leprosy
|
Phase 3 |