Cerebral Hemodynamics With rTMS in Alcohol Dependence

Study Overview
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Brief Summary
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The present study measures the cerebral hemodynamic indices of alcohol dependent patients and observe the relative changes in these parameters with rTMS application.

Detailed Description
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Alcohol abuse is a worldwide problem causing serious physical, psychological, social and economic consequences. Chronic alcohol intake has been found to increased blood viscosity, erythrocyte deformability or dehydration resulting in alterations of cerebral blood flow measures. Transcranial Doppler (TCD) sonography is a non-invasive radiological tool used for assessing the hemodynamics of the basal cerebral arteries, which can thus indirectly reflect the relative changes in regional cerebral blood flow velocity (CBFV) and vascular wall resistance. It has been used to evaluate the relative cerebral blood flow velocity changes in various psychiatric disorders like depression, schizophrenia, panic disorder, and substance use disorders including alcohol and marijuana. TCD also gives a real time assessment of the abrupt or short and long lasting effects of any external mechanical manipulation or functional stimulation of the intracranial circulation. The Mean flow velocity (MV) is the average of the edge frequency over a cardiac cycle; the edge frequency being the envelope of instantaneous peak velocities throughout the course of a cardiac cycle. Pulsatility index (PI) represents an estimate of downstream vascular resistance; low resistance vascular beds have higher diastolic flow velocities than high resistance vascular beds, hence they have low PI, and vice versa. Similarly, Resistance index (RI) is another presumptive measure of downstream vascular resistance. TCD sonography studies in alcoholism have revealed reduced mean blood flow velocities in basal cerebral arteries in chronic alcohol dependence, [1] as well as in acute stage of intoxication, but an increase after resolution of withdrawal state. [12] However, ethanol in low concentration has been found to increase the systolic, diastolic and mean blood flow velocity in middle cerebral arteries (MCA), anterior cerebral arteries (ACA) and decrease the resistance indices by reducing the cerebrovascular resistance in healthy individuals. Studies have reported that alcohol related hepatic dysfunction results in increased blood viscosity and reduced velocity in the cerebral arteries, which can be a risk factor for ischemic brain diseases. So, normalization of hemodynamic parameters is important in the prevention of possible ischemic brain diseases due to alcohol dependence. Studies evaluating cerebral hemodynamic response to rTMS application have been limited to healthy individuals, with high frequency rTMS application found to increase the cerebral blood flow velocities in both anterior and posterior basal cerebral arteries, and low frequency rTMS to temporarily decrease the blood flow velocity in ipsilateral MCA followed by an increase in the contralateral MCA. With this background, the present study was conducted to measure the cerebral hemodynamic indices of alcohol dependent patients and observe the relative changes in these parameters with rTMS application.

Official Title
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Cerebral Hemodynamics With rTMS in Alcohol Dependence: A Randomized, Sham Controlled Study

Conditions
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Alcohol Dependence

Intervention / Treatment
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* Device: Repetitive Transcranial Magnetic Stimulation (rTMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Right handed, male patients, aged between 18-60 years, with diagnosis of alcohol dependence according to DSM-IV TR, after resolution of withdrawal symptoms i.e. having Clinical Institute of Withdrawal Assessment in Alcohol Withdrawal (CIWA-Ar) score of ≤10, were included in the study. Exclusion Criteria: Patients with comorbid psychiatric, major medical or neurological disorders or with a pacemaker or metal in any part of the body were excluded from the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Healthy control<br>No Repetitive Transcranial Magnetic Stimulation (rTMS) | |
| Active Comparator: Active rTMS group<br>Active Repetitive Transcranial Magnetic Stimulation (rTMS) | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br>* The motor threshold for the left abductor pollicis brevis was determined using a figure-of-eight-shaped coil at 1 Hz frequency. Ten (over 2 weeks) rTMS sessions were administered over the right dorsolateral prefrontal cortex with an air-cooled figure-of-eight coil, angled tangentially to the head. At right DLPFC, active high-frequency (10 Hz) stimulation was administered for 4.9 seconds per train, with inter-train interval of 30 seconds, and a total of 20 trains per session. Each patient received 1000 pulses per day. The sham group was administered rTMS with the same parameters, but using a figure-of-eight sham coil.<br>|
| Sham Comparator: Sham rTMS group<br>Sham Repetitive Transcranial Magnetic Stimulation (rTMS) | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br>* The motor threshold for the left abductor pollicis brevis was determined using a figure-of-eight-shaped coil at 1 Hz frequency. Ten (over 2 weeks) rTMS sessions were administered over the right dorsolateral prefrontal cortex with an air-cooled figure-of-eight coil, angled tangentially to the head. At right DLPFC, active high-frequency (10 Hz) stimulation was administered for 4.9 seconds per train, with inter-train interval of 30 seconds, and a total of 20 trains per session. Each patient received 1000 pulses per day. The sham group was administered rTMS with the same parameters, but using a figure-of-eight sham coil.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean velocity (MV) of middle cerebral artery (MCA) and anterior cerebral artery (ACA) |  | up to 5 minutes after last (10th) rTMS session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulsatility index (PI) of middle cerebral artery (MCA) and anterior cerebral artery (ACA) |  | up to 5 minutes after last (10th) rTMS session | 
| Resistance index (RI) of middle cerebral artery (MCA) and anterior cerebral artery (ACA) |  | up to 5 minutes after last (10th) rTMS session | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rTMS, Transcranial Doppler (TCD) sonography, Cerebral hemodynamics