Clinical trial NCT03588572: The Effect of Venlafaxine on Language Function in Patients With Subcortical Aphasia: A fMRI Study
Official title: A Randomized, Single Blind, Controlled, Longitudinal Study of the Effects of Venlafaxine Hydrochloride Capsules on the Language Function of Stroke Patients With Subcortical Aphasia Using fMRI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Subcortical Aphasia
Ischemic Stroke
Keywords: Behavioural evaluation
Functional magnetic resonance imaging
Venlafaxine
Lead sponsor: Guangzhou General Hospital of Guangzhou Military Command
Sponsor class: OTHER
First posted: 2018-07-17
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
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.
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria：

* The first stroke of the left single subcortical areas, within 72hours.
* Primary school or higher level,aged between 18-75, native language Chinese
* According to the commonly used eye chart examination, the corrected visual acuity is more than 1.0.
* According to the Edinburgh Handedness Questionnaire (EHQ) as the right handed.
* The language function was normal before the onset. After the onset, the language function was mildly to moderately impaired with Western Aphasia Battery (WAB) ( Aphasia Quotient (AQ) between in 60 to 88)
* The patient cooperate with the examination, they and their guardian signed the informed consent

Exclusion Criteria：

* History of organic diseases of the nervous system and history of craniocerebral trauma.
* History of epilepsy and psychosis.
* History of material dependence.
* Decompensation of important organ function.
* Hamilton Depression Scale(HAMD )\>8 points.
* Hamilton Anxiety Scale(HAMA )\>7 points.
* The Mini-Mental State Examination (MMSE)score \<20 points.
* Dysphagia(difficult to take capsules).
* A history of allergens in component of venlafaxine.
* Pregnant women and breast-feeding women.
* Contraindication of MRI.

Primary outcomes:
measure: A Change of Outcome Measure:the Chinese Version of Western Aphasia Battery(WAB)
timeFrame: This is an outcome measure to assess the improvement of language function from onset to 3 months after treatment. Thus, participates will undergo this assessment on the first days (V1), 28±3 days (V2), and 90±3 days (V3) after randomization.
Secondary outcomes:
measure: A Change of Outcome Measure:Spontaneous Language Frequency Test(SLFT)
timeFrame: This is an outcome measure to assess the improvement of language function from onset to 3 months after treatment. Thus, participates will undergo this assessment on the first days (V1), 28±3 days (V2), and 90±3 days (V3) after randomization.
measure: A Change of Outcome Measure:Picture Naming Test(PNT)
timeFrame: This is an outcome measure to assess the improvement of language function from onset to 3 months after treatment. Thus, participates will undergo this assessment on the first days (V1), 28±3 days (V2), and 90±3 days (V3) after randomization.
measure: Follow-up Measurement: Hamilton Depression Rating Scale (HAMD)
timeFrame: We must determine that the participant is not in depression at each follow-up. Thus, participates will undergo this assessment on the first days (V1), 28±3 days (V2), and 90±3 days (V3) after randomization.
measure: Follow-up Measurement: Hamilton Anxiety Rating Scale (HAMA)
timeFrame: We must determine that the participant is not in anxiety at each follow-up. Thus, participates will undergo this assessment on the first days (V1), 28±3 days (V2), and 90±3 days (V3) after randomization.
measure: Follow-up Measurement: Mini-Mental State Examination (MMSE)
timeFrame: We must determine that the participant is not in moderate or more cognitive impairment at each follow-up. Thus, participates will undergo this assessment on the first days (V1), 28±3 days (V2), and 90±3 days (V3) after randomization.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangzhou General Hospital of Guangzhou Military Command
state: Guangdong
city: GuangZhou
country: China
facility: Cerebrovascular Department of General Hospital of Guangzhou Military Command of PLA
state: Guangdong
Study officials:
affiliation: Guangzhou General Hospital of Guangzhou Military Command
name: Liu Yan, PhD
role: STUDY_CHAIR
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