StrokePhase 2NCT02082912
NMDA Receptors in Motor Learning in Humans
A Phase 2 study testing D-cycloserine and HandMentor Pro in people with Stroke, run by Emory University at 1 site in United States.
Trial summary
The purpose of this study is to focus on enhancing upper limb recovery in patients post-stroke by using robotic-assisted therapy in combination with a drug to improve learning new motor skills. Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- Stroke
- What is being tested?
- D-cycloserine and HandMentor Pro
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2010to Apr 2012
- Phase
- Phase 2
- 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 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- between the ages of 18 and 95 years
- of either sex
- of diverse ethnic background
- have experienced a single unilateral hemispheric or brainstem stroke 3 or more months prior
- if have experienced more than one stroke, will be accepted only if all strokes are on the same side of the brain, there is no history of a clinical ischemic or hemorrhagic event affecting the other hemisphere, and there is no CT or MRI evidence of more than one a lacune or minor ischemic demyelination affecting the other hemisphere.
- active motions of the wrist and hand: 10 of wrist extension from a relaxed flexed position; 10 of extension of any two digits at any joint, and 10 of thumb extension at either joint. All active motions must be repeated 3 times within one minute.
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- passive range of motion: 90 of flexion and abduction and 45 external and internal rotation at the shoulder; 45 elbow supination and pronation; elbow extension limited by no more than 30; wrist extension to at least neutral; and digit extension limited by no more than 30.
- participants will not be required to exhibit any active shoulder or elbow motion
- ability to sit independently for at least 2 minutes
- Mini Mental Status Examination score greater than 24
- Motor Activity Log score less than 3
- Prospective participants who qualify but who have profound postural instability will undergo the intervention while walking with contact guarding or, when feasible, using their leg and more involved arm to propel a wheelchair.
- must have a score below 16 on the Center for Epidemiologic Studies Depression Scale
- must receive a score greater than 25 on the Folstein Mini Mental State Exam.
Who cannot join
- any history of more than minor head trauma, subarachnoid hemorrhage, dementia or any other neurodegenerative disease, multiple sclerosis, HIV infection, drug or alcohol abuse, serious medical illness, schizophrenia, major refractory depression
- insufficient cardiopulmonary function to participate in low-intensity sustained upper extremity exercise
- severe visual impairment
- pregnancy
- breast feeding
- participation in intensive physical therapy within the prior 12 months
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- inability to understand the potential risks and benefits of the study, personally provide informed consent, and understand and cooperate with treatment
- participating in other upper extremity rehabilitation, clinical or experimental, during the course of this trial.
- a score of less than 24 on the Folstein Mini-Mental State Exam
- a score of less than10 on the Boston Naming Test
- a first stroke less than 3 months or more than 48 months prior to the initiation of therapeutic intervention
- less than 18 years old
- clinical judgment of excessive frailty or lack of stamina
- serious uncontrolled medical conditions
- excessive pain in any joint of the more affected extremity that could limit ability to cooperate with the intervention
- passive range of motion less than 45 degrees for: abduction, flexion or external rotation at shoulder, or pronation of forearm
- greater than 30 degrees flexion contracture at any finger joint
- unable to stand independently for 2 min., transfer independently to and from the toilet or perform sit-to-stand
- current participation in other pharmacological or physical intervention studies, or have received injections of anti-spasticity drugs into upper extremity musculature within the past 3 months, or wish to have drugs injected in the foreseeable future
- receiving any anti-spasticity drugs orally at the time of expected participation
- received phenol injections less than 12 months prior to receiving therapy
- contemplating a move from proximity to the treatment site in less than 6 months from the randomization date.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to focus on enhancing upper limb recovery in patients post-stroke by using robotic-assisted therapy in combination with a drug to improve learning new motor skills.
Read the detailed description
Disability after a stroke is common, leaving 65% of patients unable to use their affected hand in daily activities after 6 months. Frequently, these limitations can cause a decreased quality of life. The current standard for intense physical therapy most commonly consists of neurofacilitation techniques and/or task-specific training. Labor-intensive and costly therapy methods are critical barriers to achieving optimal functional outcomes in stroke survivors with motor impairments. Thus, there is a great need to find new ways to enhance the effectiveness of upper limb rehabilitation in patients following stroke.
A promising approach to improving upper extremity motor function utilizing repetitive task practice (RTP) and behavioral shaping along with constraint of the less affected limb is constraint-induced movement therapy (CIMT). Two fundamental limitations of CIMT are the time necessary to deliver and oversee training and the excessive time in which the less affected limb must be constrained. RTP, in the context of CIMT appears to be effective in improving upper extremity motor function of patients with stroke. Alternative approaches such as robotic assisted therapy have been investigated. Recent evidence suggests that improvements in upper-extremity motor function, functional performance in daily tasks and quality of life are seen during a robotic-assisted physical therapy regimen.
Activation of N-methyl-D-aspartate (NMDA) receptors is important for inducing various forms of synaptic plasticity. Application of D-cycloserine (a antibiotic for treating tuberculosis) can enhance certain models of plasticity, such as long-term potentiation. Pharmacologic strategies that enhance NMDA neurotransmission and working memory represent a promising adjuvant therapy in motor rehabilitation of patients after stroke.
The researchers for this study have brought these observations together to generate a working hypothesis that D-cycloserine will enhance certain features of motor learning, information processing speed, episodic and working memory and that this effect can be coupled with physical therapy to facilitate retraining of patients to use impaired limbs to a greater extent and faster than they otherwise might be able to do. The researchers specifically hypothesize that motor (re)learning and cognition can be improved in people with post-stroke hemiparesis by increasing the excitability and synaptic activity of the motor cortex by combining D-cycloserine and robotic-assisted physical therapy.
The purpose of this study is to understand the important factors in rehabilitation therapy that help improve arm function after stroke. This information may help to ultimately reduce disability and improve quality of life in patients with stroke.
- Conditions
- Stroke
- Being tested
- D-cycloserine, Placebo, HandMentor Pro
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-cycloserineDrug
Also called Seromycin
D-cycloserine 100mg PO twice weekly (Monday and Wednesday) for three weeks
PlaceboOther
Placebo pill PO twice weekly (Monday and Wednesday) for three weeks
HandMentor ProDevice
The HandMentor Pro (Kinetic Muscles Inc.) is a robotic device that has recording electrodes. The device gives feedback during various activities requiring varying levels of wrist control. The main goal of the hand robot is to improve active range of motion about the wrist and fingers and wrist control. The robotic therapy will be done over 3 consecutive weeks for 2 hours each session (days 1, 3, 5, 8, 10, 12, 15, 17 and 19, for 18 hours total).
| Study group | Role | What they receive |
|---|---|---|
| D-cycloserine | Experimental | Subjects will take D-cycloserine and use the HandMentor Pro for robotic therapy Receives: Drug: D-cycloserine; Device: HandMentor Pro |
| Placebo | Active comparator | Subjects will take a placebo pill and use the HandMentor Pro for robotic therapy Receives: Other: Placebo; Device: HandMentor Pro |
What is being measured
The primary outcome is the main question the study is designed to answer.
Grip Strength of Affected Hand
Hand-grip strength was assessed using the whole hand and was defined as the average of 3 trials using a calibrated Jamar dynamometer (Jamar Dynamometer, Asimow Engineering Co., Santa Monica, CA), with the elbow flexed to 90º and the forearm in a neutral position. This is the standardized method for measuring hand-grip strength with a Jamar dynamometer recommended by the American Society of Hand Therapists. An increase in values means that grip strength is improving.
Measured: Baseline, Day 30
Secondary outcomes (4)
Percentage of Stroke Impact Scale (SIS) Categories Meeting Change Criteria
The percentages of Stroke Impact Scale (SIS) physical domain categories meeting criteria for Minimal Clinically Important Difference (MCID) are presented here. The SIS has 59 items in 8 domains of function where respondents rate their degree of difficulty on a 5-point scale, plus a 9th category for stroke recovery (one item, scored from 0 to 100). Scores for each domain are generated so that total scores for each domain range from 0 - 100, where higher scores indicate less difficulty and more recovery. A change of more than 4.5 to 17.8 for the domains was considered a MCID. A higher percentage of SIS categories meeting the MCID criteria indicates increased improvement in that study arm.
Measured: Baseline, Day 30
Center for Epidemiologic Studies Depression (CES-D) Scale Score
Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression (CES-D) Scale. The CES-S has 20 items rated on a scale of 0 to 3. Total scores range from 0 to 60 with higher scores indicating more depressive symptoms, and a score of 16 or above indicates depression. Baseline scores are presented in the Outcome Measure Data Table and the impact of the study arm at Day 30 is presented in the statistical analysis section.
Measured: Baseline, Day 30
Display Enhanced Testing for Concussions and Mild Traumatic Brain Injury (mTBI) (DETECT) System Score
Using a computer, helmet with heads-up-display, headphones with audio inputs, and an input unit with two buttons ("Yes" and "No"), the DETECT system combines an immersive environment with neuropsychological tests to assess mTBI. The DETECT software consists of a series of tests evaluating information processing speed, episodic memory, and working memory. Performance is scored based on response type (correct, incorrect, and missing) and response time. Test results are displayed using an internal algorithm that is based on the probability of impairment. Mean baseline z-scores are presented in the Outcome Measure Data Table and the impact of the study arm at Day 30 is presented in the statistical analysis section. A z-score of 0 represents a healthy individual; scores above 0 are the number of standard deviations above the mean, indicating more errors, taking more time, and thus having a higher probability of mild cognitive impairment.
Measured: Baseline, Day 30
Number of Blocks Moved During the Box and Block Test (BBT) of Affected Arm
Change in functional motor task performance of the arm affected by the stroke was assessed with the Box and Block Test (BBT). The BBT involves dexterous manipulation of objects and voluntary motor control, which improves with upper limb recovery following stroke. The number of blocks moved within 60 seconds are counted. Baseline scores of the mean number of blocks moved are presented in the Outcome Measure Data Table and the impact of the study arm at Day 30 is presented in the statistical analysis section.
Measured: Baseline, Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2014 (estimated)
- Study startJun 2010
- Primary completionApr 2012
- Study completionApr 2012
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 (1)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrew Butler, PhD, Emory University
- Investigators
- Andrew Bulter, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02082912
- Sponsor's protocol ID
- IRB00035176
- Other IDs
- UL1TR000454
- Status last verified
- Oct 2018
- First submitted
- 5 Mar 2014
- Last updated
- 7 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Butler AJ, Kallos J, Housley SN, LaPlaca MC, Traynelis SF, Wolf SL. Randomized, Placebo-Controlled, Double-Blind Pilot Study of D-Cycloserine in Chronic Stroke. Rehabil Res Pract. 2015;2015:534239. doi: 10.1155/2015/534239. Epub 2015 Oct 26.
PubMed 26587287
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NMDA Receptors in Motor Learning in Humans
- ClinicalTrials.gov ID
- NCT02082912
- Acronym / sponsor ID
- IRB00035176
- Conditions
- Stroke
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Jun 2010
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 10 Mar 2014 (estimated)
- Results
- Posted 22 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to focus on enhancing upper limb recovery in patients post-stroke by using robotic-assisted therapy in combination with a drug to improve learning new motor skills.
Detailed description
Disability after a stroke is common, leaving 65% of patients unable to use their affected hand in daily activities after 6 months. Frequently, these limitations can cause a decreased quality of life. The current standard for intense physical therapy most commonly consists of neurofacilitation techniques and/or task-specific training. Labor-intensive and costly therapy methods are critical barriers to achieving optimal functional outcomes in stroke survivors with motor impairments. Thus, there is a great need to find new ways to enhance the effectiveness of upper limb rehabilitation in patients following stroke.
A promising approach to improving upper extremity motor function utilizing repetitive task practice (RTP) and behavioral shaping along with constraint of the less affected limb is constraint-induced movement therapy (CIMT). Two fundamental limitations of CIMT are the time necessary to deliver and oversee training and the excessive time in which the less affected limb must be constrained. RTP, in the context of CIMT appears to be effective in improving upper extremity motor function of patients with stroke. Alternative approaches such as robotic assisted therapy have been investigated. Recent evidence suggests that improvements in upper-extremity motor function, functional performance in daily tasks and quality of life are seen during a robotic-assisted physical therapy regimen.
Activation of N-methyl-D-aspartate (NMDA) receptors is important for inducing various forms of synaptic plasticity. Application of D-cycloserine (a antibiotic for treating tuberculosis) can enhance certain models of plasticity, such as long-term potentiation. Pharmacologic strategies that enhance NMDA neurotransmission and working memory represent a promising adjuvant therapy in motor rehabilitation of patients after stroke.
The researchers for this study have brought these observations together to generate a working hypothesis that D-cycloserine will enhance certain features of motor learning, information processing speed, episodic and working memory and that this effect can be coupled with physical therapy to facilitate retraining of patients to use impaired limbs to a greater extent and faster than they otherwise might be able to do. The researchers specifically hypothesize that motor (re)learning and cognition can be improved in people with post-stroke hemiparesis by increasing the excitability and synaptic activity of the motor cortex by combining D-cycloserine and robotic-assisted physical therapy.
The purpose of this study is to understand the important factors in rehabilitation therapy that help improve arm function after stroke. This information may help to ultimately reduce disability and improve quality of life in patients with stroke.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D-cycloserine | Experimental | Drug: D-cycloserine, Device: HandMentor ProSubjects will take D-cycloserine and use the HandMentor Pro for robotic therapy |
| Placebo | Active comparator | Other: Placebo, Device: HandMentor ProSubjects will take a placebo pill and use the HandMentor Pro for robotic therapy |
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- between the ages of 18 and 95 years
- of either sex
- of diverse ethnic background
- have experienced a single unilateral hemispheric or brainstem stroke 3 or more months prior
- if have experienced more than one stroke, will be accepted only if all strokes are on the same side of the brain, there is no history of a clinical ischemic or hemorrhagic event affecting the other hemisphere, and there is no CT or MRI evidence of more than one a lacune or minor ischemic demyelination affecting the other hemisphere.
Key exclusion criteria (22 listed)
- any history of more than minor head trauma, subarachnoid hemorrhage, dementia or any other neurodegenerative disease, multiple sclerosis, HIV infection, drug or alcohol abuse, serious medical illness, schizophrenia, major refractory depression
- insufficient cardiopulmonary function to participate in low-intensity sustained upper extremity exercise
- severe visual impairment
- pregnancy
- breast feeding
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 |
|---|---|---|
| D-cycloserineAlso: SeromycinD-cycloserine 100mg PO twice weekly (Monday and Wednesday) for three weeks | Drug | D-cycloserine |
| PlaceboPlacebo pill PO twice weekly (Monday and Wednesday) for three weeks | Other | Placebo |
| HandMentor ProThe HandMentor Pro (Kinetic Muscles Inc.) is a robotic device that has recording electrodes. The device gives feedback during various activities requiring varying levels of wrist control. The main goal of the hand robot is to improve active range of motion about the wrist and fingers and wrist control. The robotic therapy will be done over 3 consecutive weeks for 2 hours each session (days 1, 3, 5, 8, 10, 12, 15, 17 and 19, for 18 hours total). | Device | D-cycloserine, Placebo |
Primary outcome
Grip Strength of Affected Hand
Time frame: Baseline, Day 30
Hand-grip strength was assessed using the whole hand and was defined as the average of 3 trials using a calibrated Jamar dynamometer (Jamar Dynamometer, Asimow Engineering Co., Santa Monica, CA), with the elbow flexed to 90º and the forearm in a neutral position. This is the standardized method for measuring hand-grip strength with a Jamar dynamometer recommended by the American Society of Hand Therapists. An increase in values means that grip strength is improving.
4 secondary outcomes
Percentage of Stroke Impact Scale (SIS) Categories Meeting Change Criteria
Time frame: Baseline, Day 30
Center for Epidemiologic Studies Depression (CES-D) Scale Score
Time frame: Baseline, Day 30
Display Enhanced Testing for Concussions and Mild Traumatic Brain Injury (mTBI) (DETECT) System Score
Time frame: Baseline, Day 30
Number of Blocks Moved During the Box and Block Test (BBT) of Affected Arm
Time frame: Baseline, Day 30
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26587287Butler AJ, Kallos J, Housley SN, LaPlaca MC, Traynelis SF, Wolf SL. Randomized, Placebo-Controlled, Double-Blind Pilot Study of D-Cycloserine in Chronic Stroke. Rehabil Res Pract. 2015;2015:534239. doi: 10.1155/2015/534239. Epub 2015 Oct 26.
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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.
Andrew Bulter, PhD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing D-cycloserine and HandMentor Pro in people with Stroke, run by Emory University at 1 site in United States.
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 14 inclusion and 22 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 7 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Apr 2015). 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?
Grip Strength of Affected Hand (time frame: Baseline, Day 30). 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 NCT02082912, which also lists 1 linked publication.
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 7 Nov 2018; AzTrials last refreshed its copy on 6 Nov 2026.