Treating Intention In Aphasia: Neuroplastic Substrates

• Sponsor: University of Florida (Other)
• Overall Status: Completed
• CT.gov ID: NCT00567242
• Collaborator: National Institute on Deafness and Other Communication Disorders (NIDCD) (NIH)
• Enrollment: 14
• Locations: 3
• Arms: 2
• Duration (Months): 30.1
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if an "intentional act" improves treatment response for patients with nonfluent aphasia. The treatment involves naming pictures and saying members of categories. The "intentional act" requires initiating picture naming or category member trials with a left-hand movement sequence. Nonfluent aphasia is a disorder of language production in which patients with damage to the brain's language system have trouble initiating and maintaining spoken communication. All patients participating in the study take part in functional MRI scans to determine how treatments affect brain systems.

Condition or Disease	Intervention/Treatment	Phase
Aphasia; Cerebrovascular Accident	Behavioral: Word-finding with intention component; Behavioral: Word-finding with no intention component	Phase 1/Phase 2

Detailed Description

A new treatment manipulating intention substrates for language production in "nonfluent" aphasia patients was developed. The intention component involves initiating word-finding trials with a complex left-hand movement. The study addresses (1) whether or not the intention manipulation (complex left-hand movement) makes a unique contribution to treatment outcome and (2) whether or not the intention manipulation helps to shift word production mechanisms from the left to the right frontal lobe. All study participants take part in functional magnetic resonance imaging (fMRI) scans of word-finding before and after treatment and at 3-month follow-up to measure changes in lateralization of frontal lobe activity during word finding. Only patients with a substantial degree of left frontal activity on the pre-treatment fMRI scan can participate. There are three specific aims: (1) to determine if repetitive initiation of word production with a complex left-hand movement leads to increased right-hemisphere lateralization of frontal activity and if these changes can be attributed to the intention component of treatment, (2) to determine whether activity in posterior perisylvian cortices that is entrained to right frontal activity shows a greater increase in right-hemisphere lateralization from pre- to post-treatment fMRI when the intention component is included in treatment, and (3) to determine whether onset of hemodynamic responses (HDRs) in right motor/premotor cortex becomes more closely associated with the temporal onset of participants' spoken responses across treatment when the intention component is included in treatment. If successful, the treatment can provide a new treatment vehicle for increasing language function in patients with "nonfluent" aphasia.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Treating Intention In Aphasia: Neuroplastic Substrates
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Word-finding with intention component Treats word-finding (picture naming, category member generation) with an intention manipulation (complex left-hand movement to initiate word-finding trials)	Behavioral: Word-finding with intention component; Word-finding trials (picture-naming) with intention manipulation (initiating word-finding trials with a complex left-hand movement). 8 (or more) baseline sessions over 4 days followed by 30 treatment sessions (2 sessions/day, 5 days/week for 3 weeks).; Other Names: Intention Treatment
Active Comparator: Word-finding with no intention component Word-finding trials similar to intention mediated treatment, but without intention manipulation	Behavioral: Word-finding with no intention component; Word-finding trials with no intention manipulation. 8 (or more) baseline sessions in 4 days followed by 30 treatment sessions (2 sessions/day, 5 days/week for 3 weeks).; Other Names: Control Treatment

Outcome Measures

Primary Outcome Measures

1. Lateralization of Frontal Lobe (and Posterior Perisylvian) Activity During Word Production [immediately post-treatment scan minus pre-treatment baseline scan]

   Functional MRI laterality indices (LIs)were calculated for lateral frontal, medial frontal, and posterior perisylvian cortex regions of interest (ROIs): L=number of active voxels in left hemisphere ROI and R=number of active voxels in right hemisphere ROI using the following formula: (L-R)/(L+R). LIs could vary from -1 (completely right lateralized) to +1 (completely left lateralized). Then, change in LIs was calculated by subtracting the pre-treatment from the post-treatment and 3-mo follow-up LI. It was expected the intention manipulation would show a rightward shift in LI.

Secondary Outcome Measures

1. Picture Naming Probe Scores (% Accuracy) [trend for time series of 8 baseline + 30 treatment sessions]

   Improvement for the time series from 8 baseline sessions through 30 treatment sessions for naming probes was computed with the C statistic using Tryon's (1982, 1983) formula for each subject. C statistics were converted to Z scores, using the formula provided by Tryon (1982). Z scores indicated treatment change for each subject, with a positive and significant Z score indicating substantive treatment gains. Z scores were then compared between groups with a t statistic. It was expected that the intention manipulation would lead to greater treatment gains than when it was not used.

2. Category Member Generation Probe Scores (% Accuracy) [trend for time series of 8 baseline + 30 treatment sessions]

   Improvement for the time series from 8 baseline sessions through 30 treatment sessions for naming probes was computed with the C statistic using Tryon's (1982, 1983) formula for each subject. C statistics were converted to Z scores, using the formula provided by Tryon (1982). Z scores indicated treatment change for each subject, with a positive and significant Z score indicating substantive treatment gains. Z scores were then compared between groups with a t statistic. It was expected that the intention manipulation would lead to greater treatment gains than when it was not used.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 95 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Nonfluent aphasia caused by stroke

• Moderate to severe word-finding problems

• 6 or more months post stroke

• Right handed prior to stroke

• All strokes in left hemisphere

• Native English speaker

• Capable of following verbal directions

Exclusion Criteria:

• Severe impairment of word comprehension

• Brain injury or disease in addition to stroke

• Drug or alcohol abuse within past 6 months

• Schizophrenia or other psychiatric disorder necessitating hospitalization

• History of learning disability

• Claustrophobia

• Cardiac pace-maker

• Ferrous metal implants not attached to bone, metal fragments in body

• Profound hearing loss

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida	Gainesville	Florida	United States	32610
2	University of Florida/Shands Hospital	Jacksonville	Florida	United States	32209
3	Brooks Center for Rehabilitation Studies	Jacksonville	Florida	United States	32216

Sponsors and Collaborators

• University of Florida
• National Institute on Deafness and Other Communication Disorders (NIDCD)

Investigators

• Principal Investigator: Bruce Crosson, PhD, University of Florida

Study Documents (Full-Text)

None provided.

More Information

Publications

• Conway T, Heilman KM, Gopinath K, Peck K, Bauer R, Briggs RW, Torgesen JK, Crosson B. Neural substrates related to auditory working memory comparisons in dyslexia: an fMRI study. J Int Neuropsychol Soc. 2008 Jul;14(4):629-39. doi: 10.1017/S1355617708080867.
• Crosson B, Fabrizio KS, Singletary F, Cato MA, Wierenga CE, Parkinson RB, Sherod ME, Moore AB, Ciampitti M, Holiway B, Leon S, Rodriguez A, Kendall DL, Levy IF, Rothi LJ. Treatment of naming in nonfluent aphasia through manipulation of intention and attention: a phase 1 comparison of two novel treatments. J Int Neuropsychol Soc. 2007 Jul;13(4):582-94. Epub 2007 May 18.
• Crosson B, McGregor K, Gopinath KS, Conway TW, Benjamin M, Chang YL, Moore AB, Raymer AM, Briggs RW, Sherod MG, Wierenga CE, White KD. Functional MRI of language in aphasia: a review of the literature and the methodological challenges. Neuropsychol Rev. 2007 Jun;17(2):157-77. Epub 2007 May 25. Review.
• Gopinath K, Crosson B, McGregor K, Peck K, Chang YL, Moore A, Sherod M, Cavanagh C, Wabnitz A, Wierenga C, White K, Cheshkov S, Krishnamurthy V, Briggs RW. Selective detrending method for reducing task-correlated motion artifact during speech in event-related FMRI. Hum Brain Mapp. 2009 Apr;30(4):1105-19. doi: 10.1002/hbm.20572.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT00567242
• Other Study ID Numbers: R01DC007387-01A1; R01DC007387
• First Posted: Dec 4, 2007
• Last Update Posted: May 3, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by University of Florida: aphasia; therapies, investigational; rehabilitation of speech and language disorders; magnetic resonance imaging, functional; language
• Additional relevant MeSH terms: Aphasia; Stroke

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from December 2006 through August 2009. Fourteen subjects with minimally nonfluent aphasia, anomia, and at least some degree of frontal lesion participated in the study.
Pre-assignment Detail	Prior to trial assignment, subjects underwent a functional MRI scan to determine degree of lateralization of frontal activity during word generation. Subjects with a high degree of right frontal lateralization of activity were excluded. Further, patients whose naming scores indicated that they were no more than minimally anomic were excluded.

Arm/Group Title	Word-finding With Intention Manipulation	Word-finding With no Intention Manipulation
Arm/Group Description	Treats word-finding (picture naming, category member generation) with an intention manipulation (complex left-hand movement to initiate word-finding trials)	Word-finding trials similar to intention mediated treatment, but without intention manipulation
Period Title: Overall Study
STARTED	7	7
COMPLETED	7	7
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Word-finding With Intention Manipulation	Word-finding With no Intention Manipulation	Total
Arm/Group Description	Treats word-finding (picture naming, category member generation) with an intention manipulation (complex left-hand movement to initiate word-finding trials)	Word-finding trials similar to intention mediated treatment, but without intention manipulation	Total of all reporting groups
Overall Participants	7	7	14
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 28.6%	5 71.4%	7 50%
>=65 years	5 71.4%	2 28.6%	7 50%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.86 (12.35)	63.00 (9.22)	66.93 (11.24)
Sex: Female, Male (Count of Participants)
Female	4 57.1%	1 14.3%	5 35.7%
Male	3 42.9%	6 85.7%	9 64.3%
Region of Enrollment (participants) [Number]
United States	7 100%	7 100%	14 100%

Outcome Measures

1. Primary Outcome

Title	Lateralization of Frontal Lobe (and Posterior Perisylvian) Activity During Word Production
Description	Functional MRI laterality indices (LIs)were calculated for lateral frontal, medial frontal, and posterior perisylvian cortex regions of interest (ROIs): L=number of active voxels in left hemisphere ROI and R=number of active voxels in right hemisphere ROI using the following formula: (L-R)/(L+R). LIs could vary from -1 (completely right lateralized) to +1 (completely left lateralized). Then, change in LIs was calculated by subtracting the pre-treatment from the post-treatment and 3-mo follow-up LI. It was expected the intention manipulation would show a rightward shift in LI.
Time Frame	immediately post-treatment scan minus pre-treatment baseline scan

Outcome Measure Data

Analysis Population Description

Data for all subjects completing the protocol for their respective arm were analyzed.

Arm/Group Title	Word-finding With Intention Manipulation	Word-finding With no Intention Manipulation
Arm/Group Description	Treats word-finding (picture naming, category member generation) with an intention manipulation (complex left-hand movement to initiate word-finding trials)	Word-finding trials similar to intention mediated treatment, but without intention manipulation
Measure Participants	7	7
Mean (Standard Deviation) [laterality index]	-0.2802 (0.1077)	-0.1832 (0.2768)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Word-finding With Intention Manipulation
	Comments	H1: The Intention Group will show a significant rightward shift in lateral frontal laterality from pre-treatment to post-treatment. H0: The Intention Group will show no shift in lateral frontal laterality from pre-treatment to post-treatment. Since this is a repeated measures t test, the data are presented as the mean and standard deviation for for the post-treatment laterality index minus the pre-treatment laterality index.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2801
	Confidence Interval	(1-Sided) 95%; to -0.0709
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1077
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Word-finding With no Intention Manipulation
	Comments	H1: The Control Group will show a significant rightward shift in lateral frontal lateral indices from pre-treatment to post-treatment. H0: The Control group will show no shift in lateral frontal laterality indices from pre-treatment to post-treatment. Since the analysis to test these hypotheses is a repeated-measures t-test, the mean and standard deviation are given for post-treatment laterality index minus pre-treatment laterality index.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1832
	Confidence Interval	(1-Sided) 95%; to 0.3546
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2768
	Estimation Comments

2. Secondary Outcome

Title	Picture Naming Probe Scores (% Accuracy)
Description	Improvement for the time series from 8 baseline sessions through 30 treatment sessions for naming probes was computed with the C statistic using Tryon's (1982, 1983) formula for each subject. C statistics were converted to Z scores, using the formula provided by Tryon (1982). Z scores indicated treatment change for each subject, with a positive and significant Z score indicating substantive treatment gains. Z scores were then compared between groups with a t statistic. It was expected that the intention manipulation would lead to greater treatment gains than when it was not used.
Time Frame	trend for time series of 8 baseline + 30 treatment sessions

Outcome Measure Data

Analysis Population Description

Data from all subjects completing their respective arms were analyzed, with the exception that one control subject was eliminated because of an unstable baseline measure.

Arm/Group Title	Word-finding With Intention Manipulation	Word-finding With no Intention Manipulation
Arm/Group Description	Treats word-finding (picture naming, category member generation) with an intention manipulation (complex left-hand movement to initiate word-finding trials)	Word-finding trials similar to intention mediated treatment, but without intention manipulation
Measure Participants	7	6
Mean (Standard Deviation) [Z score]	3.68 (1.61)	3.92 (1.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Word-finding With Intention Manipulation, Word-finding With no Intention Manipulation
	Comments	H1: The Intention Group would show more improvement across treatment than the Control Group. H0: The Intention Group and the Control Group would not show any difference in improvement across treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.24
	Confidence Interval	(1-Sided) 95%; -1.81 to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.88
	Estimation Comments

3. Secondary Outcome

Title	Category Member Generation Probe Scores (% Accuracy)
Description	Improvement for the time series from 8 baseline sessions through 30 treatment sessions for naming probes was computed with the C statistic using Tryon's (1982, 1983) formula for each subject. C statistics were converted to Z scores, using the formula provided by Tryon (1982). Z scores indicated treatment change for each subject, with a positive and significant Z score indicating substantive treatment gains. Z scores were then compared between groups with a t statistic. It was expected that the intention manipulation would lead to greater treatment gains than when it was not used.
Time Frame	trend for time series of 8 baseline + 30 treatment sessions

Outcome Measure Data

Analysis Population Description

Data from all subjects completing their respective arms were analyzed, with the exception of one control subject whose baseline was not stable.

Arm/Group Title	Word-finding With Intention Manipulation	Word-finding With no Intention Manipulation
Arm/Group Description	Treats word-finding (picture naming, category member generation) with an intention manipulation (complex left-hand movement to initiate word-finding trials)	Word-finding trials similar to intention mediated treatment, but without intention manipulation
Measure Participants	7	6
Mean (Standard Deviation) [Z score]	3.50 (0.83)	1.94 (1.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Word-finding With Intention Manipulation, Word-finding With no Intention Manipulation
	Comments	H1: The Intention Group would show more improvement across treatment than the Control Group. H0: The Intention Group and the Control Group would not show any difference in improvement across treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.56
	Confidence Interval	(1-Sided) 95%; 0.26 to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.73
	Estimation Comments

Adverse Events

Time Frame	Baseline to 3-month follow-up
Arm/Group Title	Word-finding With Intention Manipulation		Word-finding With no Intention Manipulation
Arm/Group Description	Treats word-finding (picture naming, category member generation) with an intention manipulation (complex left-hand movement to initiate word-finding trials)		Word-finding trials similar to intention mediated treatment, but without intention manipulation
All Cause Mortality
	Word-finding With Intention Manipulation		Word-finding With no Intention Manipulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Word-finding With Intention Manipulation		Word-finding With no Intention Manipulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Word-finding With Intention Manipulation		Word-finding With no Intention Manipulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/7 (0%)

Limitations/Caveats

Patients who had aphasia were enrolled. Groups were equated for anomia severity, but not type of aphasia. Aphasia types were not evenly distributed between groups which may affect results. Intention subjects were older than Control Subjects.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.