Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05903079 |
| Other study ID # |
20220596 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 5, 2023 |
| Est. completion date |
January 10, 2025 |
Study information
| Verified date |
June 2023 |
| Source |
Hospital de Clinicas de Porto Alegre |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Fibromyalgia (FM) is a syndrome characterized by generalized musculoskeletal pain, fatigue,
non-restorative sleep, cognitive alterations, depressive and neurovegetative symptoms.
Conventional pharmacological therapies are known to produce responses with little clinical
impact in more than 50% of patients. Functional alterations of the motor cortex and its
connections with subcortical structures have also been demonstrated in FM. Based on the
above, the objective of this research is to identify subgroups of patients with greater
potential for response to treatment with a view to advancing diagnosis and treatment. In this
study, the therapeutic target will be transcranial direct current stimulation (tDCS)
according to the potential of responsiveness to the placebo effect, with the precise location
of the stimulation area by a neuronavigation system, with the objective of counter-regulating
the processes dysfunctional factors responsible for triggering and maintaining FM symptoms.
Therefore, this clinical trial aims to compare the effectiveness of anodic tDCS applied in
the left dorsolateral prefrontal cortex (DLPFC) compared to sham tDCS in FM, according to
susceptibility to the placebo effect and serum endorphin levels.
Description:
Fibromyalgia (FM) is a chronic disease that affects more than five million people annually in
the US. The population prevalence ranges from 2% to 5.4% according to the 2010 American
Society of Rheumatology diagnostic criteria. The female: male ratio has changed according to
the diagnostic criteria. When applying the 1990 diagnostic criteria (ACR 1990) it is 7:1 and
according to the 2010 criteria (ACR 2010) and revised in 2016, this ratio is 2.3:1.
Regardless of the variation in prevalence between the sexes, it is a syndrome characterized
by generalized musculoskeletal pain, fatigue, non-restorative sleep, cognitive changes,
depressive symptoms and other correlates of autonomic dysfunction, such as colon syndrome.
irritability and bladder tenesmus. In addition, FM has a level of psychological distress
associated with catastrophism and depressive symptoms, which can worsen the prognosis and
reinforce disability more markedly than is observed in other chronic pain conditions. FM is
the prototype of dysfunction syndromes that course with pain by processes mediated by the
central and peripheral nervous system. Patients with FM have been associated with an
increased risk of stroke. In fact, it is a syndrome with great social impact, which demands
advances in the understanding of diagnostic and therapeutic processes. In this direction, an
attempt has been made to identify factors associated with the potential for response to
treatment: potential for response to placebo, clinical, psychological, neurophysiological
factors, levels of endorphins and neurotrophins associated with clinical response. The quest
to understand the effects of these markers aims to personalize therapy and identify factors
that can modify the clinical effect of treatments and the organization of neurobiological
systems.
Although the results with the use of tDCS have been promising in the treatment of several
chronic pain conditions, as demonstrated in a recent meta-analysis conducted by the Pain and
Neuromodulation research group at Hospital de Clínicas de Porto Alegre (Zortea et al., 2019).
) it is necessary to consider that expectations about pain can directly affect nociceptive
processing. Such expectations contribute to the placebo effect that has been shown to be
mediated by opioids. The study by Eippert et al. (2009) showed that naloxone administration
reduces the neural and behavioral effects of placebo, as well as placebo-induced responses in
several cortical and subcortical areas that constitute the descending pain modulatory system
(e.g., rACC, PAG, RVM, and hypothalamus). ). Furthermore, it abolished the rACC-PAG coupling
induced by the placebo intervention. The expectation of placebo-induced analgesia is
positively correlated with the availability of MOR. On the contrary, negative suggestion
reduces the analgesic effects of synthetic opiates. All these findings support the close
association between opioids and expectations that drive placebo-mediated analgesia.
Therefore, this clinical trial aims to compare the effectiveness of anodic tDCS applied to
the left dorsolateral prefrontal cortex (DLPFC) compared to sham tDCS in FM, according to
susceptibility to the placebo effect and serum endorphin levels, in the following results (
1) treatment efficacy, which includes daily measurements recorded in a Brief Pain Inventory
(BPI) application, which allows assessing pain from a multidimensional perspective (pain
intensity and interference with general activities, mood, mobility, work, personal
relationships, sleep and enjoyment of life, etc.) (primary outcome), the primary outcome will
be the Brief Pain Inventory (BPI) score, which assesses pain levels, sleep quality, mood,
fatigue, disability, use of analgesics, etc. Secondary outcomes are the impact of pain on
quality of life, depressive symptoms. Predictors of the placebo effect will also be
evaluated, through the Verbal Numerical Pain Scale (NPS, 0-10) scores in the last week and
through the BPI scores, using a multiple hierarchical model. Among potential predictors,
there is disability due to pain, psychological profile, drugs in use. In addition to these,
the index of inflammatory markers (serum interleukins IL1-, IL-6, IL-10; TNF-alpha and
C-reactive protein); serum levels of endorphins, brain-derived neurotrophic factor (BDNF),
S-100B protein and the polymorphisms Val66Met of the BDNF gene and Val158Met of the COMT
enzyme gene. Will be included 100 women with FM, randomized to receive active (n=50) or sham
(n=50) tDCS, aged between 18 and 65 years. Randomization will be stratified according to the
placebo effect response potential, determined after a simulated tDCS session. A variation in
NPS (0-10) equal to or greater than 30% after a simulated tDCS session will classify them as
high responders to the placebo effect. The follow-up time will be four weeks after a single
treatment session. In this way, it is intended to produce consistent evidence for the use of
this low-cost technique in the treatment of patients of the Unified Health System, which will
be directed to patients with chronic pain at the same time, which will provide data to
subsidize the feasibility of studying the effect of this complementary therapy in other
conditions, such as refractory depression and neurorehabilitation. In addition, to provide
data to better understand tDCS response predictors in outcomes that are related to the impact
of pain on the quality of life of conditions that generate a lot of suffering and high costs
to the health system.
