Clinical trial NCT05596058: Non-pharmacological Treatments in Migraine.
Official title: Efficacy of a Non-pharmacological Treatments on Neurophysiological and Clinical Outcomes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Migraine
Keywords: Migraine
Habituation
Sensitization
transcranial Magnetic stimulation
Lead sponsor: University of Trieste
Sponsor class: OTHER
First posted: 2022-10-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: We are going to use a simple randomization scheme 1:1:1 with excel and assign subjects into three groups respectively: 15 patients in physical-cognitive tasks groups, 15 patients in active exercise Only and 15 patients in Cognitive training.
Primary purpose: TREATMENT

Brief summary: Migraine may have an adverse effect on physical, cognitive, and psychosocial functioning. It causes major consequences for the quality of life of the sufferer and a major burden on the health care system.

About the physiopathology, two opposing processes, depression (habituation) and facilitation (sensitization), determine the final behavioural outcome after a sequence of repetitive stimuli.

Sensitization is a general behavioural response of augmentation to innocuous sensory and noxious stimuli. It has been associated with a dysfunction in descending pain inhibition.

The nature or intensity of a painful event does not strongly relate to the development of chronic pain, but an individual's behavioural response to the event contributes to chronicity. Imaging data have identified that chronic pain may change the structure of the brain in response to environmental demands.

It suggests that the brain of healthy control has a "healthy response" to frequent nociceptive input, such as "habituation", while chronic pain patients show a "maladaptive plasticity".

Habituation is "a response decrement as a result of repeated stimulation". It is a phenomenon observed in the autonomic and behavioural component called the "orienting response" in humans. The orienting response is elicited when a novel stimulus is encountered, and it directs attention toward that stimulus. When the same stimulus is presented repeatedly occur habituation. Researchers have found a number of physiological mechanisms associated with Orienting response. Habituation of the orienting response is a simple form of learning and acts an attentional filtering mechanism that makes people able to select what is part of their present goal and adapt to environment. In this way only one channel of information to be processed, with the rest filtered out. Habituation depends on a memory process whereby the organism learns to associate goal irrelevant stimuli with a no-consequence response.

Lack of Habituation during stimulus repetition is a functional property of the brain in people with migraine between attacks. Thalamo-cortical dysrhythmia and lack of H characterize migraineurs' brains. This abnormal information processing increases during the pain-free days, the vertex is just before the attack, and decreases in the ictal phase. Migraineurs are characterized by a generally increased sensitivity to visual (sensitivity to light), auditory (to sound), or somatic stimuli not only during the attack, but also outside of the attack.

It was confirmed also by analysing motor cortex excitability. Aerobic exercises may be effective as pharmacological treatment in the management of migraine and focused attention task may help human subjects to better ignore irrelevant stimuli.

The main aim of this study is to assess the efficacy of a non-pharmacological treatment, such as physical therapy, with a specific dual task protocol of active exercise with concomitant cognitive tasks, in relation to habituation (Transcranial magnetic stimulation) and sensitization (Algometer assessment) neurophysiological outcomes. The second aim is to assess these non-pharmacological treatments concerning to clinical outcomes (intensity of pain, duration of attacks and frequency of pain; neurophysiological test on executive functions).

Detailed description: A Randomized Controlled Trial (RCT) will be conducted on three groups of patients with migraine. The project was approved by the institutional review board C.E.U.R. . Patients will be recruited and randomized by the Neurologic Clinic, Headache Centre (University of Trieste in the Department of Medical, Surgical, and Health Sciences), diagnosing Migraine after a neurologic visit (diagnostic criteria of ICDH3-beta).

In the first enrollment visit (T0), the patients will be undergone anamnestic evaluation, neurological and general objective examination. The following criteria of exclusion are going to be respected: pregnancy; serious psychiatric pathologies, serious pathologies as traumas, cancers or infective pathologies, important surgery procedures during the last year; physiotherapy and other no pharmacological treatment for another pathology; less than 18 years of age; presence of multiple migraine; presence of therapeutics changes linked to headache in the last 3 months; absence of pharmacological prophylaxis treatment in the last 3 months; no auditory or visual processing disorders. While, the criteria of inclusion are going to be the following: diagnosis migraine (diagnostic criteria of ICDH3-beta); Age over 18. Patients are going to be given a diary for cephalic outcome: frequency (headache days a month), intensity and duration of attack. The paper diary is going to inserted into a specific database for subsequent data analysis.

All patients are going to re-evaluated with the diary after one month (T1). The frequency is going to be between 15 days a month and 18 days a month. Transcranial magnetic Stimulation is going to be recorded.The Migraine disability assessment scale (MIDAS) will be performed. The MIDAS questionnaire consist of five questions aimed at assessing the impact of migraine on the patients' daily life in the 3 months prior to the study, in terms of absence from work or school, inability to carry out household chores, or take part in family, social, or leisure activities expressed in days. The final score was obtained by adding up the total number of days for each of the five questions.

Simple randomization scheme 1:1:1 was used with excel and assign subjects into three groups respectively: 15 patients in physical-cognitive tasks groups, 15 patients in active exercise Only and 15 patients in Cognitive task only. All patient going to sign the informed consent.

Patients will be allowed to take symptomatic medications in case of severe headache according to guidelines of the International Headache Society. Patients will be only asked to limit symptomatic medications consumption for a maximum twice per week in order to not affect the interpretation of data. Finally, after three months of treatment, the final visit will be performed (T2) with clinical re-evaluation of the patients and analysis of the cephalic parameters reported in the diary, the data of transcranial magnetic stimulation and the headache-related disability with MIDAS.

All patients will be reexamined at 1 months follow up (T3) with the diary, Transcranial magnetic stimulation and MIDAS.

Eligibility criteria: Inclusion Criteria:

* diagnosis migraine (diagnostic criteria of ICDH3-beta)
* Age over 18

Exclusion Criteria:

* pregnancy
* serious psychiatric pathologies
* serious pathologies as traumas, cancers or infective pathologies
* important surgery procedures during the last year
* physiotherapy and other no pharmacological treatment for another pathology
* less than 18 years of age;
* presence of multiple migraine
* presence of therapeutics changes linked to headache in the last 3 months
* absence of pharmacological prophylaxis treatment in the last 3 months
* no auditory or visual processing disorders

Primary outcomes:
measure: Values of Transcranial magnetic stimulation in migraine patients
timeFrame: Before each treatment
measure: Change from Baseline of the values of Transcranial magnetic stimulation in migraine patients at 3 months
timeFrame: 3 months
measure: Change from baseline of the value of Transcranial magnetic stimulation in migraine patients at 4 months
timeFrame: 4 months
Secondary outcomes:
measure: Headache parameters and MIDAS
timeFrame: Before each treatment
measure: Headache parameters and MIDAS
timeFrame: 3 months of each treatment
measure: Headache parameters and MIDAS
timeFrame: 4 months
measure: Algometer Assessment
timeFrame: Before each treatment
measure: Algometer Assessment
timeFrame: 3 months of each treatment
measure: Algometer Assessment
timeFrame: 4 months
Other outcomes:
measure: Neuropsychological tests
timeFrame: Before each treatment
measure: Neuropsychological tests
timeFrame: 3 months of each treatment
measure: Neuropsychological tests
timeFrame: 4 months
measure: Neuropsychological tests
timeFrame: Before each treatment
Locations:
city: Trieste
country: Italy
facility: Manuela Deodato
state: TS
Study officials:
References: