The Effect of Venlafaxine on Language Function in Patients With Subcortical Aphasia: A fMRI Study
Condition: Subcortical Aphasia; Ischemic Stroke
MeSH terms: Ischemic Stroke; Aphasia
Study type: Interventional

Summary: 
      Previous studies have demonstrated that venlafaxine significantly improves the language
      function of healthy subjects and increase of fMRI activation in cortical language area. This
      study was designed to investigate the relationship between venlafaxine on the cortical
      language functional reorganization and clinical language improvements in the stroke patients
      with subcortical aphasia.

      It is a randomized, controlled, single-blind, longitudinal trial which has approved by the
      ethics committee of Guangzhou General Hospital of Guangzhou Military Command, and all
      patients and their guardian should sign an informed consent. The patients will divide into
      the venlafaxine group and the control group according to the principle of randomization
      (random number table). The patients in the venlafaxine group begin to take a venlafaxine
      hydrochloride capsule after enrollment ( each containing venlafaxine 75mg), qd, until 4 weeks
      after randomization, and the control group do not. Assessments of language functional
      behavior and examines of functional magnetic resonance imaging (fMRI) should be performed on
      the first days (V1), 28±3 days (V2) and 90±3 days (V3) after randomization.

      Through all this procession, we expect improve the language function of participants in
      experiment and clarify its mechanism,the research may help develop a new treatment for other
      patients with similar conditions.
    

Detailed description: 
      The cases will recruit from inpatients with acute ischemic stroke in Department of
      Cerebrovascular disease, The Guangzhou General Hospital of Guangzhou Military Command from
      June 2018 to June 2019. The diagnose of ischemic stroke is made using the diagnostic criteria
      of the International Association of Neurological Diseases and Stroke Association in 1982. The
      classification criteria for subcortical ischemic stroke are based on the current
      international TOAST etiological classification method.

      It is a randomized, controlled, single-blind, longitudinal trial which has approved by the
      ethics committee of Guangzhou General Hospital of Guangzhou Military Command, and all
      patients and their guardian should sign an informed consent. The patients will divide into
      the venlafaxine group and the control group according to the principle of randomization
      (random number table). The patients in the venlafaxine group begin to take a venlafaxine
      hydrochloride capsule after enrollment ( each containing venlafaxine 75mg), qd, until 4 weeks
      after randomization, and the control group do not. Assessments of language functional
      behavior and examines of functional magnetic resonance imaging (fMRI) should be performed on
      the first days (Visit1,V1), 28±3 days (Visit2, V2) and 90±3 days (Visit3, V3) after
      randomization. Language functional behavioral assessments included the Chinese version of
      Western Aphasia Battery(WAB), spontaneous language frequency test(SLFT) and picture naming
      test(PNT). Examines of fMRI included task-state fMRI and resting-state fMRI. All patients
      received language rehabilitation training (twice a week, one hour each) which will be
      conducted by a professional rehabilitation physiotherapist from the Visitation1 until the end
      of Visitation3. The blood pressure and heart rate of each patient will be monitored and
      recorded on each visit, and two routine blood tests are performed at V0 and V3, including the
      blood routine and the liver and kidney function.

      The test sample quantity is estimated using the sample size estimated by the professional
      software nQuery Advisor7.0. According to the main evaluation index of the effect of the
      previous literature on the efficacy of venlafaxine, the experimental group and the control
      group are 7.5±3.8 and 4.3±2.6，The standard deviation will be 3.26, and 0.05 will be the
      statistical meaning level (double tail). The test efficiency will be set to 0.83. The balance
      design will be used to estimate the sample size of the experimental group and the control
      group in 16 cases. In addition, considering the 20% missing rate, a total of 45 samples will
      be included in the study.

      Task-state fMRI: an fMRI block design will be adopted, and DMDX software will be used to
      present each picture in series alternated between baseline (B) and activation (A)
      [B-A-B-A-B…]. Thirty-six animal pictures and 36 tool pictures accurately recognized by all
      subjects will be selected from the Snodgrass picture database. Six blocks of animal naming
      and six blocks of tool naming will be repeated, and each block continued for 18s with six
      pictures.the block-design diagram of picture naming task. The abstract figure of an American
      skunk which is unrecognized by all the subjects will be selected for baseline of animal
      naming. A schematic drawn arrow will be chosen for baseline picture of tool naming.Patients
      will be required to silently name the object in each picture without moving their lips. To
      avoid practice effects, the pictures used for activation will be different from those used in
      the behavioral evaluation. In the baseline phase, the participants will be asked to identify
      the orientation of the pictures by silently saying "upright" or "inverted." The subjects will
      receive task familiarization training prior to the test to ensure that there will be no
      substantive picture naming but only positional judgment in the baseline task.

      Rest-state fMRI: During the rest-state fMRI scan, no task instruction will be given to the
      patient, and the patient will be completely relaxing, closing his eyes, breathing calmly,
      keeping his head still, but can not fall asleep, try to avoid any systematic thinking
      activities, scanning 8min.

      Functional magnetic resonance data acquisition

      The cranial brain scan will be performed using the US GE Signa HDx 3.0T Tesla superconducting
      magnetic resonance imaging system. The scanning sequence and parameters are as follows:

        1. T1 structure imaging using FSPGR BRAVO sequence. The parameters included: time of
           repetition, 8.86 ms; time of echo, 3.52 ms; field of view, 24×24 cm2; in-plane
           resolution,256×256; slice thickness, 1 mm;interslice gap, 1 mm; and number of slices,
           176.

        2. Echo-Planar Imaging (EPI) is used to acquire task-state fMRI data.The parameters
           included: time of repetition, 3000ms; time of echo, 40 ms; field of view, 24×24 cm2;
           in-plane resolution,64×64; slice thickness, 4 mm; interslice gap, 1 mm; and number of
           slices, 34. Scan a sequence of 240s, a total of 12 min.

        3. Echo-Planar Imaging (EPI) is used to acquire rest-state fMRI data.The parameters
           included: time of repetition, 3000ms; time of echo, 40 ms; field of view, 24×24 cm2;
           in-plane resolution,64×64; slice thickness, 4 mm; interslice gap, 1 mm; and number of
           slices, 34. A total of 8 min.
    

Intervention name(s): Venlafaxine hydrochloride capsules
Intervention type(s): Drug
Intervention description(s): The patients in venlafaxine group begin to take the venlafaxine hydrochloride capsules after the first visitation(the first day after randomization), each containing venlafaxine 75mg, 1 capsule per day, until 4 weeks after randomization
Other intervention name(s): EFFEXOR XR®
Intervention MeSH terms: Venlafaxine Hydrochloride
Allocation: Randomized
Intervention model: Factorial Assignment
Intervention model description: On the basis of conventional clinical treatment in both groups, the experimental group was given drug intervention, and the control group was not given drug treatment.
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Behavioural evaluation; Functional magnetic resonance imaging; Venlafaxine