Subcortical AphasiaNCT03588572
The Effect of Venlafaxine on Language Function in Patients With Subcortical Aphasia: A fMRI Study
A study testing Venlafaxine hydrochloride capsules in people with Subcortical Aphasia and Ischemic Stroke, run by Guangzhou General Hospital of Guangzhou Military Command at 2 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Subcortical Aphasia, Ischemic Stroke
- What is being tested?
- Venlafaxine hydrochloride capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 2 sitesChina
- Study dates
- 1 Aug 2018to 1 Aug 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
China2 sites
Guangzhou General Hospital of Guangzhou Military Command
Guangzhou, Guangdong, 510000
Cerebrovascular Department of General Hospital of Guangzhou Military Command of PLA
Guangzhou, Guangdong, 510010
About this 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
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.
Read the 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:
- 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.
- 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.
- 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.
- Conditions
- Subcortical Aphasia, Ischemic Stroke
- Being tested
- Venlafaxine hydrochloride capsules
- Keywords
- Behavioural evaluation, Functional magnetic resonance imaging, Venlafaxine
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Venlafaxine hydrochloride capsulesDrug
Also called EFFEXOR XR®
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
| Study group | Role | What they receive |
|---|---|---|
| Venlafaxine Group | Experimental | The patients in venlafaxine group begin to take the venlafaxine hydrochloride capsules after the first visitation ( each containing venlafaxine 75mg), 1 capsule per day, until 4 weeks after randomization. Receives: Drug: Venlafaxine hydrochloride capsules |
| Controlled group | No intervention | the patients in controlled group do not use the drug during the experiment, and the other treatments are same as the venlafaxine group. |
What is being measured
The primary outcome is the main question the study is designed to answer.
A Change of Outcome Measure:the Chinese Version of Western Aphasia Battery(WAB)
The main outcome measure for this scale is Aphasia Quotient(AQ) which mainly tests the ability of spontaneous speech, oral comprehension, repetition, and naming, and reflects the severity of aphasia, and can be used as a reliable indicator to evaluate the improvement and deterioration of aphasia. Score fluctuation is 0-100 points, the normal value is 98.4-100 points, AQ<93.8 can be judged as language dysfunction.
Measured: 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 (5)
A Change of Outcome Measure:Spontaneous Language Frequency Test(SLFT)
This test mainly assesses spontaneous speech fluency of participants.It requires participants name as many food names as possible within one minute, and each correct one to give one point.The higher the score, the better the language function.
Measured: 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.
A Change of Outcome Measure:Picture Naming Test(PNT)
This test mainly assesses the ability of picture name of participants.we used a program for displaying named pictures on a computer screen (60 photos in total, of which 20 were Chinese celebrity faces). Each image was displayed in 3 seconds, and 1 point was correctly named for an image.The faces of celebrities were selected from the picture database of Chinese celebrities in the State Key Laboratory of Cognitive Neuroscience and Learning at Beijing Normal University.Score fluctuation is 0-60 points, the higher the score, the better the ability of picture name.
Measured: 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.
Follow-up Measurement: Hamilton Depression Rating Scale (HAMD)
The Hamilton Depression Rating Scale (HAMD) has proven useful for many years as a way of determining a patient's level of depression before, during, and after treatment. It generally takes 15-20 minutes to complete the interview and score the results. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine items are scored from 0-2. HAMD Scoring Instructions:0-7=Normal, 8-13 = Mild Depression, 14-18 = Moderate Depression, 19-22 = Severe Depression, ≥ 23 = Very Severe Depression(i.e.,Minimum 0 points and maximum 50 points, the higher the score, the greater the likelihood of depression).
Measured: 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.
Follow-up Measurement: Hamilton Anxiety Rating Scale (HAMA)
The Hamilton Anxiety Rating Scale (HAMA) is a widely used and well-validated tool for measuring the severity of a patient's anxiety. The HAMA is composed of 14 items and takes 15-20 minutes to complete the interview and score the results. Each item is scored on a 5-point scale, ranging from 0=not present to 4=severe.HAMA Scoring Instructions:0-8=Normal, 8-13= Possible Anxiety, 14-17 = Mild Anxiety, 18-24 = Moderate Anxiety, 25-30 = Severe Anxiety(i.e.,the higher the score, the greater the likelihood of anxiety).
Measured: 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.
Follow-up Measurement: Mini-Mental State Examination (MMSE)
The Mini-Mental State Examination (MMSE) is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. Administration of the test takes between 5 and 10 minutes. The MMSE test includes simple questions and problems in a number of areas: the time and place of the test, repeating lists of words, arithmetic such as the serial sevens, language use and comprehension, and basic motor skills. Any score greater than or equal to 24 points (out of 30) indicates a normal cognition. Below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment.The raw score may also need to be corrected for educational attainment and age.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2018
- Study start1 Aug 2018
- Primary completion1 Jul 2019
- Study completion1 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (32)Papers the sponsor has linked to this study.
- Other trials for Subcortical AphasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- 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 blind
- Who is masked
- Participant
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Guangzhou General Hospital of Guangzhou Military Command
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yan Liu, Guangzhou General Hospital of Guangzhou Military Command
- Investigators
- Liu Yan, PhD, Study chair, Guangzhou General Hospital of Guangzhou Military Command
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03588572
- Sponsor's protocol ID
- LY-81471172
- Status last verified
- Sep 2021
- First submitted
- 13 Jun 2018
- Last updated
- 13 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pedersen PM, Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS. Aphasia in acute stroke: incidence, determinants, and recovery. Ann Neurol. 1995 Oct;38(4):659-66. doi: 10.1002/ana.410380416.
PubMed 7574464Dickey L, Kagan A, Lindsay MP, Fang J, Rowland A, Black S. Incidence and profile of inpatient stroke-induced aphasia in Ontario, Canada. Arch Phys Med Rehabil. 2010 Feb;91(2):196-202. doi: 10.1016/j.apmr.2009.09.020.
PubMed 20159121Berthier ML. Poststroke aphasia : epidemiology, pathophysiology and treatment. Drugs Aging. 2005;22(2):163-82. doi: 10.2165/00002512-200522020-00006.
PubMed 15733022Engelter ST, Gostynski M, Papa S, Frei M, Born C, Ajdacic-Gross V, Gutzwiller F, Lyrer PA. Epidemiology of aphasia attributable to first ischemic stroke: incidence, severity, fluency, etiology, and thrombolysis. Stroke. 2006 Jun;37(6):1379-84. doi: 10.1161/01.STR.0000221815.64093.8c. Epub 2006 May 11.
PubMed 16690899Luria AR, Simernitskaya EG, Tubylevich B. The structure of psychological processes in relation to cerebral organization. Neuropsychologia. 1970 Jan;8(1):13-9. doi: 10.1016/0028-3932(70)90022-9. No abstract available.
PubMed 5522545Kim YH, You SH, Ko MH, Park JW, Lee KH, Jang SH, Yoo WK, Hallett M. Repetitive transcranial magnetic stimulation-induced corticomotor excitability and associated motor skill acquisition in chronic stroke. Stroke. 2006 Jun;37(6):1471-6. doi: 10.1161/01.STR.0000221233.55497.51. Epub 2006 May 4.
PubMed 16675743Debonnel G, Saint-Andre E, Hebert C, de Montigny C, Lavoie N, Blier P. Differential physiological effects of a low dose and high doses of venlafaxine in major depression. Int J Neuropsychopharmacol. 2007 Feb;10(1):51-61. doi: 10.1017/S1461145705006413. Epub 2006 May 11.
PubMed 16690006Berrocoso E, Mico JA. Role of serotonin 5-HT1A receptors in the antidepressant-like effect and the antinociceptive effect of venlafaxine in mice. Int J Neuropsychopharmacol. 2009 Feb;12(1):61-71. doi: 10.1017/S1461145708008766. Epub 2008 Apr 14.
PubMed 18405417Beique J, de Montigny C, Blier P, Debonnel G. Effects of sustained administration of the serotonin and norepinephrine reuptake inhibitor venlafaxine: II. In vitro studies in the rat. Neuropharmacology. 2000 Jul 24;39(10):1813-22. doi: 10.1016/s0028-3908(00)00018-6.
PubMed 10884562Thase ME, Entsuah AR, Rudolph RL. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry. 2001 Mar;178:234-41. doi: 10.1192/bjp.178.3.234.
PubMed 11230034Nemeroff CB, Entsuah R, Benattia I, Demitrack M, Sloan DM, Thase ME. Comprehensive analysis of remission (COMPARE) with venlafaxine versus SSRIs. Biol Psychiatry. 2008 Feb 15;63(4):424-34. doi: 10.1016/j.biopsych.2007.06.027. Epub 2007 Sep 24.
PubMed 17888885Thase ME, Entsuah R, Cantillon M, Kornstein SG. Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions. J Womens Health (Larchmt). 2005 Sep;14(7):609-16. doi: 10.1089/jwh.2005.14.609.
PubMed 16181017Schmitt AB, Bauer M, Volz HP, Moeller HJ, Jiang Q, Ninan PT, Loeschmann PA. Differential effects of venlafaxine in the treatment of major depressive disorder according to baseline severity. Eur Arch Psychiatry Clin Neurosci. 2009 Sep;259(6):329-39. doi: 10.1007/s00406-009-0003-7. Epub 2009 Mar 3.
PubMed 19255709Bauer M, Tharmanathan P, Volz HP, Moeller HJ, Freemantle N. The effect of venlafaxine compared with other antidepressants and placebo in the treatment of major depression: a meta-analysis. Eur Arch Psychiatry Clin Neurosci. 2009 Apr;259(3):172-85. doi: 10.1007/s00406-008-0849-0. Epub 2009 Jan 22.
PubMed 19165525Rickels K, Mangano R, Khan A. A double-blind, placebo-controlled study of a flexible dose of venlafaxine ER in adult outpatients with generalized social anxiety disorder. J Clin Psychopharmacol. 2004 Oct;24(5):488-96. doi: 10.1097/01.jcp.0000138764.31106.60.
PubMed 15349004
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03588572
- Acronym / sponsor ID
- LY-81471172
- Conditions
- Subcortical Aphasia, Ischemic Stroke
- Keywords
- Behavioural evaluation, Functional magnetic resonance imaging, Venlafaxine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Guangzhou General Hospital of Guangzhou Military CommandUniversity, hospital or other
- Study start
- 1 Aug 2018 (actual)
- Primary completion
- 1 Jul 2019 (actual)
- Study completion
- 1 Aug 2019 (actual)
- First posted
- 17 Jul 2018 (actual)
- Results
- Posted 3 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (participant)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Venlafaxine Group | Experimental | Drug: Venlafaxine hydrochloride capsulesThe patients in venlafaxine group begin to take the venlafaxine hydrochloride capsules after the first visitation ( each containing venlafaxine 75mg), 1 capsule per day, until 4 weeks after randomization. |
| Controlled group | No intervention | –the patients in controlled group do not use the drug during the experiment, and the other treatments are same as the venlafaxine group. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Venlafaxine hydrochloride capsulesAlso: EFFEXOR XR®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 | Drug | Venlafaxine Group |
Primary outcome
A Change of Outcome Measure:the Chinese Version of Western Aphasia Battery(WAB)
Time frame: 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.
The main outcome measure for this scale is Aphasia Quotient(AQ) which mainly tests the ability of spontaneous speech, oral comprehension, repetition, and naming, and reflects the severity of aphasia, and can be used as a reliable indicator to evaluate the improvement and deterioration of aphasia. Score fluctuation is 0-100 points, the normal value is 98.4-100 points, AQ<93.8 can be judged as language dysfunction.
5 secondary outcomes
A Change of Outcome Measure:Spontaneous Language Frequency Test(SLFT)
Time frame: 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.
A Change of Outcome Measure:Picture Naming Test(PNT)
Time frame: 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.
Follow-up Measurement: Hamilton Depression Rating Scale (HAMD)
Time frame: 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.
Follow-up Measurement: Hamilton Anxiety Rating Scale (HAMA)
Time frame: 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.
Follow-up Measurement: Mini-Mental State Examination (MMSE)
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 7574464Pedersen PM, Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS. Aphasia in acute stroke: incidence, determinants, and recovery. Ann Neurol. 1995 Oct;38(4):659-66. doi: 10.1002/ana.410380416.
- Background: PubMed 20159121Dickey L, Kagan A, Lindsay MP, Fang J, Rowland A, Black S. Incidence and profile of inpatient stroke-induced aphasia in Ontario, Canada. Arch Phys Med Rehabil. 2010 Feb;91(2):196-202. doi: 10.1016/j.apmr.2009.09.020.
- Background: PubMed 15733022Berthier ML. Poststroke aphasia : epidemiology, pathophysiology and treatment. Drugs Aging. 2005;22(2):163-82. doi: 10.2165/00002512-200522020-00006.
- Background: PubMed 16690899Engelter ST, Gostynski M, Papa S, Frei M, Born C, Ajdacic-Gross V, Gutzwiller F, Lyrer PA. Epidemiology of aphasia attributable to first ischemic stroke: incidence, severity, fluency, etiology, and thrombolysis. Stroke. 2006 Jun;37(6):1379-84. doi: 10.1161/01.STR.0000221815.64093.8c. Epub 2006 May 11.
- Background: PubMed 5522545Luria AR, Simernitskaya EG, Tubylevich B. The structure of psychological processes in relation to cerebral organization. Neuropsychologia. 1970 Jan;8(1):13-9. doi: 10.1016/0028-3932(70)90022-9. No abstract available.
- Background: PubMed 16675743Kim YH, You SH, Ko MH, Park JW, Lee KH, Jang SH, Yoo WK, Hallett M. Repetitive transcranial magnetic stimulation-induced corticomotor excitability and associated motor skill acquisition in chronic stroke. Stroke. 2006 Jun;37(6):1471-6. doi: 10.1161/01.STR.0000221233.55497.51. Epub 2006 May 4.
- Background: PubMed 16690006Debonnel G, Saint-Andre E, Hebert C, de Montigny C, Lavoie N, Blier P. Differential physiological effects of a low dose and high doses of venlafaxine in major depression. Int J Neuropsychopharmacol. 2007 Feb;10(1):51-61. doi: 10.1017/S1461145705006413. Epub 2006 May 11.
- Background: PubMed 18405417Berrocoso E, Mico JA. Role of serotonin 5-HT1A receptors in the antidepressant-like effect and the antinociceptive effect of venlafaxine in mice. Int J Neuropsychopharmacol. 2009 Feb;12(1):61-71. doi: 10.1017/S1461145708008766. Epub 2008 Apr 14.
- Background: PubMed 10884562Beique J, de Montigny C, Blier P, Debonnel G. Effects of sustained administration of the serotonin and norepinephrine reuptake inhibitor venlafaxine: II. In vitro studies in the rat. Neuropharmacology. 2000 Jul 24;39(10):1813-22. doi: 10.1016/s0028-3908(00)00018-6.
- Background: PubMed 11230034Thase ME, Entsuah AR, Rudolph RL. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry. 2001 Mar;178:234-41. doi: 10.1192/bjp.178.3.234.
- Background: PubMed 17888885Nemeroff CB, Entsuah R, Benattia I, Demitrack M, Sloan DM, Thase ME. Comprehensive analysis of remission (COMPARE) with venlafaxine versus SSRIs. Biol Psychiatry. 2008 Feb 15;63(4):424-34. doi: 10.1016/j.biopsych.2007.06.027. Epub 2007 Sep 24.
- Background: PubMed 16181017Thase ME, Entsuah R, Cantillon M, Kornstein SG. Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions. J Womens Health (Larchmt). 2005 Sep;14(7):609-16. doi: 10.1089/jwh.2005.14.609.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Liu Yan, PhD study chair
Guangzhou General Hospital of Guangzhou Military Command
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Venlafaxine hydrochloride capsules in people with Subcortical Aphasia and Ischemic Stroke, run by Guangzhou General Hospital of Guangzhou Military Command at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A Change of Outcome Measure:the Chinese Version of Western Aphasia Battery(WAB) (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03588572, which also lists 32 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2021.