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Methylphenidate Treatment of Attention Deficits in Epilepsy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kimford Jay Meador, Stanford University
ClinicalTrials.gov Identifier:
NCT02178995
First received: June 24, 2014
Last updated: July 19, 2016
Last verified: July 2016
  Purpose

Methylphenidate (MPH) has long been used to improve attention and cognitive difficulties associated with ADHD, including in children with ADHD and epilepsy (Torres et al., 2008). Methylphenidate (MPH) is also helpful in treating attention and other cognitive difficulties in a variety of other neurological and medical conditions (Kajs-Wyllie, 2002; Prommer, 2012). We seek to evaluate the potential efficacy and safety of this medication in treating attention deficits, as well as other cognitive difficulties, experienced by adult patients with epilepsy.

To our knowledge, there are currently very few studies which explicitly examine the impact of MPH on measureable attention deficits and other cognitive deficits in adult patients with epilepsy. We hope to quantify what impact, if any, methylphenidate has on attention, in addition to other specific measureable cognitive functions, in patients with cognitive complaints and epilepsy, and contribute to a growing body of evidence which supports the safety of methylphenidate's use for attention deficits in patients with epilepsy. As other effective treatments for attention and other cognitive difficulties in patients with epilepsy are not currently available, MPH could represent an important option in the treatment of such patients.


Condition Intervention Phase
Epilepsy
Cognitive Deficits
Attention Deficits
Drug: Methylphenidate
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Methylphenidate Treatment of Attentional and Cognitive Deficits in Epilepsy

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Conners' Continuous Performance Test (CPT) (Double-blind Portion, Primary Variables) [ Time Frame: difference in scores on specific variables between MPH 20mg, 10mg, and placebo (randomized to administration at weeks 2, 3, or 4) ] [ Designated as safety issue: No ]

    Scores on this test measure attentiveness/vigilance and response time. Primary measures are: D', HRTSD D' represents 'detectability,' and is a derived statistic which measures a participant's ability to distinguish target stimuli from non-target stimuli, and incorporates response time and accuracy factors. The equation for deriving it is proprietary to the test which markets the CPT. A higher, or less negative, score is considered WORSE.

    HRTSD represents the standard deviation of participant hit reaction time data, as measured for a variety of different stimuli types across the trial. It is a measure of the participant's ability to maintain attention across the trial. A higher score represents more variability and is considered WORSE.


  • Symbol-digit Matching Test (Double-blind Portion) [ Time Frame: Difference in scores between MPH 20mg, 10mg, or placebo during double-blind portion during which medication was randomized to weeks 2, 3, or 4. ] [ Designated as safety issue: No ]
    Symbol-digit matching test is a measure processing speed and working memory. The task involves matching nonsense symbols with numbers based on a key as quickly as possible within 90s. Score represents the number of correct responses within the time frame. Minimum score is 0. There is not a meaningful 'maximum' score, as there are too many symbols for a participant to successfully complete within the allotted time. A higher score is better.

  • MCG Paragraph Memory Test (Double-blind Portion) [ Time Frame: Difference in scores between MPH 20mg, 10mg, or placebo, randomized to be given at weeks 2, 3, or 4 ] [ Designated as safety issue: No ]
    MCG paragraph memory test is a measure of verbal memory. Participants are read aloud a long, detailed story, and are then asked to immediately repeat all information they can remember from the story. Each pertinent story element (as pre-defined on a key) is considered 1 correct response. Minimum score is 0, maximum is 100. A higher score is better.

  • Conners CPT Outcomes (Primary Variables) (Open-Label Portion) [ Time Frame: Difference between scores at baseline (visit 1) and on methylphenidate open-label (visit 5), compared to untreated healthy controls ] [ Designated as safety issue: No ]

    Within-groups comparison (between visit 1 and visit 5 within patients with epilepsy, comparing scores at baseline to scores on methylphenidate) as well as a comparison against healthy controls who repeated the cognitive measures an equal number of times (to assess and control for test/retest and placebo improvements).

    D' represents 'detectability,' and is a derived statistic which measures a participant's ability to distinguish target stimuli from non-target stimuli, and incorporates response time and accuracy factors. The equation for deriving it is proprietary to the test which markets the CPT. A higher, or less negative, score is considered WORSE.

    HRTSD represents the standard deviation of participant hit reaction time data, as measured for a variety of different stimuli types across the trial. It is a measure of the participant's ability to maintain attention across the trial. A higher score represents more variability and is considered WORSE.


  • Symbol-digit Matching Test (Open Label Phase) [ Time Frame: The single-dose double blind phase was followed by an open-label 4-week treatment phase. ] [ Designated as safety issue: No ]
    Symbol-digit matching test is a measure processing speed and working memory. The task involves matching nonsense symbols with numbers based on a key as quickly as possible within 90s. Score represents the number of correct responses within the time frame. Minimum score is 0. There is not a meaningful 'maximum' score, as there are too many symbols for a participant to successfully complete within the allotted time. A higher score is better.

  • MCG (Open-label Portion) [ Time Frame: The single-dose double blind phase was followed by an open-label 4-week treatment phase. ] [ Designated as safety issue: No ]
    MCG paragraph memory test is a measure verbal memory. Participants are read aloud a long, detailed story, and are then asked to immediately repeat all information they can remember from the story. Each pertinent story element (as pre-defined on a key) is considered 1 correct response. Minimum score is 0, maximum is 100. A higher score is better.

  • Seizure Frequency (Open-label Portion) [ Time Frame: Randomized portion is followed by 1-month open-label portion. ] [ Designated as safety issue: Yes ]
    Seizures per 28 'at-risk' days. This is a comparison of 28 days prior to baseline visit as compared to seizure rate while taking methylphenidate, adjusted to provide a 'number of seizures per 28 days' measurement.

  • QOLIE-89 Aggregate Score [ Time Frame: Change from baseline to end of methylphenidate open label treatment (end month 2) ] [ Designated as safety issue: No ]

    QOLIE-89 is a questionnaire to assess quality of life and subjective cognitive effects. The aggregate score is the overall calculated score. Note: most of its questions are specific to patients with epilepsy, and therefore the questionnaire cannot be validly completed by healthy controls. Therefore, only participants with epilepsy completed the questionnaire.

    QOLIE aggregate scores and subscale scores are calculated based on individual patient responses throughout the survey, and according to scoring rules as determined by the creator of the questionnaire. Scores are rated 0 (worst) to 100 (best).



Secondary Outcome Measures:
  • CPT Scores (Double-blind Portion) (Secondary Variables) [ Time Frame: Difference between scores on MPH 20mg, 10mg, or placebo during randomized visits weeks 2, 3, or 4 ] [ Designated as safety issue: No ]

    Secondary variables in CPT: hits, omissions, commissions

    "Hits" represents the raw number of accurate responses to target stimuli, out of a maximum of 288. A higher number is better.

    "Omissions" are errors committed when a target stimuli is not appropriately responded to. A higher number is worse. Theoretically, the maximum number of omissions would be 288. A lower number is BETTER.

    "Commissions" are errors committed when a participant responds to a non-target stimuli. Because a participant may make multiple such errors for a given stimuli, there is no raw maximum. A lower number is BETTER.


  • Seizure Frequency/Severity (Double-blind Portion) [ Time Frame: Seizure rate during 28 days prior to study compared to during randomized, single-dose portion, rate adjusted to seizures per 28 patient days. ] [ Designated as safety issue: Yes ]
    Seizures per 28 'at-risk' days. This is a comparison of 28 days prior to baseline visit as compared to seizure rate while taking methylphenidate, adjusted to provide a 'number of seizures per 28 days' measurement.

  • QOLIE-89 Selected Cognitive Subscales (Open-label) [ Time Frame: Comparing baseline (visit 1) to end of open-label (end of week 8) ] [ Designated as safety issue: No ]

    Pre-selected secondary variables were cognitive subscales on the QOLIE-89 felt likely to be affected by MPH: attention/concentration; memory; language; energy/fatigue.

    QOLIE aggregate scores and subscale scores are calculated based on individual patient responses throughout the survey, and according to scoring rules as determined by the creator of the questionnaire. Scores are rated 0 (worst) to 100 (best).


  • CPT Outcomes (Secondary Variables) (Open-label Portion) [ Time Frame: Baseline (Visit 1) vs end of Open-label (week 8) ] [ Designated as safety issue: No ]

    Omissions, commissions, and hits

    "Hits" represents the raw number of accurate responses to target stimuli, out of a maximum of 288. A higher number is better.

    "Omissions" are errors committed when a target stimuli is not appropriately responded to. A higher number is worse. Theoretically, the maximum number of omissions would be 288. A lower number is BETTER.

    "Commissions" are errors committed when a participant responds to a non-target stimuli. Because a participant may make multiple such errors for a given stimuli, there is no raw maximum. A lower number is BETTER.



Other Outcome Measures:
  • Adverse Events Profile (Open-Label) [ Time Frame: Baseline (Visit 1) vs end of Open-label (week 8) ] [ Designated as safety issue: Yes ]

    This is a side-effects reporting scale for anti-epileptic medications. Because it encompasses cognitive and non-cognitive side effects, it was not considered one of our main cognitive/quality of life outcomes of interest. It is used in other studies of AED side effects, however, so was included.

    The scale consists of 19 symptoms rated 1 (Never a problem) to 4 (Always or often a problem). Minimum score is 19, maximum score is 76. A higher score is WORSE.


  • Stimulant Side-effects Checklist [ Time Frame: Baseline (Visit 1) vs end of Open-label (week 8) ] [ Designated as safety issue: Yes ]

    This is a questionnaire covering common stimulant side-effects, intended to help monitor for any significant or common adverse effects.

    The scale lists 16 common stimulant side effects rated 0 (absent) to 9 (serious). Minimum score is 0, maximum is 144. A higher score is WORSE.


  • Neuropsychiatric Questionnaires [ Time Frame: Baseline (Visit 1) vs end of Open-label (week 8) ] [ Designated as safety issue: No ]

    Beck Depression Inventory, Beck Anxiety Inventory, Apathy Evaluation Scale. These were not primary or secondary variables of interest given methylphenidate's primary expected action being on cognition. Included given one author's interest, as other studies suggesting psychiatric improvements (particularly apathy and depression) with methylphenidate.

    BDI is a common clinical and research measure of depression. It has 21 questions and is scored 0 (no depression) to 63 (most severe depression). A higher score is worse.

    BAI is a measure of anxiety, which also has 21 questions and is scored 0 (no anxiety) to 63 (most severe anxiety). A higher score is worse.

    AES is a measure of clinical apathy, and is an 18-item scale. It rates symptoms as "not at all," "slightly," "somewhat," or "a lot," which are then converted to numerical values 1 (least apathy) to 4 (most apathy). Scores range from 18 (no apathy) to 72 (most apathy).



Enrollment: 55
Study Start Date: August 2014
Study Completion Date: December 2015
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Healthy Controls

Healthy controls completed the same neurocognitive batteries and neuropsychiatric questionnaires as individuals with epilepsy, but were not exposed to study medication.

Healthy controls were included primarily for use in the open-label comparison. They did not receive blinded medication during the 'double-blind' portion and their data was not used in the 'double-blind' comparison. In order to control for test/re-test variables, they completed testing during the 'double-blind' portion, so that they completed testing an equivalent number of times to the epilepsy patients in the 'open-label' portion.

Experimental: Participants With Epilepsy (Open-label)
Following the final randomized visit, interested participants were prescribed 10mg of methylphenidate twice daily, increased to 20mg of methylphenidate twice daily as tolerated. After a four week treatment trial, their scores on the batteries and questionnaires were again assessed.
Drug: Methylphenidate

Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Other Name: Ritalin
Experimental: 10mg, 20mg, Then Placebo (Double-blind)

Participants received three single doses in randomized order of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and completed cognitive testing and neuropsychiatric questionnaires. This single-dose phase was followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy first received blinded, single-dose capsules which contained either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate. At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Drug: Methylphenidate

Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Other Name: Ritalin
Experimental: 10mg, Placebo, Then 20mg (Double-blind)

Participants received three single doses in randomized order of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and completed cognitive testing and neuropsychiatric questionnaires. This single-dose phase was followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy first received blinded, single-dose capsules which contained either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate. At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Drug: Methylphenidate

Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Other Name: Ritalin
Experimental: Placebo, 20mg, Then 10mg (Double-blind)

Participants received three single doses in randomized order of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and completed cognitive testing and neuropsychiatric questionnaires. This single-dose phase was followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy first received blinded, single-dose capsules which contained either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate. At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Drug: Methylphenidate

Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Other Name: Ritalin
Experimental: Placebo, 10mg, Then 20mg (Double-blind)

Participants received three single doses in randomized order of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and completed cognitive testing and neuropsychiatric questionnaires. This single-dose phase was followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy first received blinded, single-dose capsules which contained either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate. At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Drug: Methylphenidate

Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Other Name: Ritalin
Experimental: 20mg, Placebo, Then 10mg (Double-blind)

Participants received three single doses in randomized order of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and completed cognitive testing and neuropsychiatric questionnaires. This single-dose phase was followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy first received blinded, single-dose capsules which contained either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate. At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Drug: Methylphenidate

Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Other Name: Ritalin
Experimental: 20mg, 10mg, Then Placebo - Double-blind

Participants received three single doses in randomized order of blinded medication, either a placebo, 20mg of methylphenidate, or 10mg of methylphenidate, and completed cognitive testing and neuropsychiatric questionnaires. This single-dose phase was followed by an open-label 4-week treatment trial of methylphenidate.

Methylphenidate: Participants with epilepsy first received blinded, single-dose capsules which contained either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate. At each visit, they received one capsule and then completed the neurocognitive batteries and neuropsychiatric questionnaires. There was no medication administered between visits during this time.

Drug: Methylphenidate

Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Other Name: Ritalin
Experimental: 40mg, 20mg, Then Placebo (One Participant)
This study was originally intended to use 40mg, 20mg, and placebo doses rather than 20mg, 10mg, and placebo. This individual developed tachycardia (see adverse events) on the 40mg dose, and was withdrawn from the double-blind portion as a result. We removed the 40mg doses from this study and replaced them with 10mg doses. No other participant received a 40mg dose. This participant rejoined the open-label portion after consultation with his PCP due to significant perceived benefit from the MPH dose.
Drug: Methylphenidate

Participants with epilepsy will first receive blinded, single-dose capsules which contain either:

Placebo 20mg of methylphenidate or 10mg of methylphenidate.

At each visit, they will receive one capsule and then complete the neurocognitive batteries and neuropsychiatric questionnaires. There will be no medication administered between visits during this time. Following the final randomized visit, interested participants will be prescribed 10mg of methylphenidate twice daily, to be increased to 20mg of methylphenidate twice daily. After four weeks, their scores on the batteries and questionnaires will again be assessed.

Other Name: Ritalin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. For participants with seizures:

    • H/o seizures of any cause
    • Subjective cognitive complaints
    • Stable antiepileptic drug doses which are not expected to change during the study
    • Recent normal cardiac auscultation (may be done prior to enrollment by personal physician or study staff)
    • Neurologist's judgement that participant is clinically appropriate for this study
  2. For healthy volunteers

    • No history of seizures or other neurological disorders
    • No history of cognitive complaints for any reason (including ADHD)
    • Not on any medications which would interfere w/ cognitive testing
  3. English fluency

Exclusion Criteria:

  1. IQ
  2. History of an adverse reaction to methylphenidate
  3. Age >65 or <18
  4. Personal medical history of

    1. Arrhythmias,
    2. Structural cardiac disease,
    3. Other cardiac abnormality
    4. Uncontrolled hypertension (>150/95) during study. For those with BP >140/90 & <150/95, they will be monitored during the study and refer them for treatment if their BP remains elevated throughout the study.
    5. Uncontrolled tachycardia during study
    6. Progressive neurological disorders which may interfere w/ cognition for reasons other than seizures
    7. Glaucoma
    8. Other medical or neurological illnesses or symptoms which may interfere with cognition or medication (e.g., severe liver or renal disease, active infections, etc), or which make use of the medication inappropriate (e.g., severe agitation/anxiety).
    9. Intellectual disability sufficient to render a participant unable to consent
    10. Status epilepticus within the last year
    11. Neurosurgery which would be expected to interfere with study tasks within the last 6 months.
  5. Substance use history

    1. Met criteria for substance use disorder within the past year
    2. Active illicit substance use
    3. Alcohol use meeting criteria for substance abuse
    4. Unwillingness to abstain from alcohol w/in 24 hours of testing
  6. Personal psychiatric history

    1. History of a primary psychotic disorder, such as schizophrenia, or mania.
    2. History of suicide attempts within the last year
    3. Active suicidality
  7. Severe cognitive impairments (e.g. aphasia) which render a participant unable to consent
  8. Currently receiving medications which would be expected to interfere with the study tasks, if they cannot be held for study visits;
  9. Pregnancy or active breastfeeding;
  10. Women of childbearing potential who are sexually active and not willing or able to use a contraceptive strategy during the course of the study.
  11. Any other factor which may interfere w/ a participant's ability to consent or to complete the required cognitive tasks, or may significantly interfere with their performance on the required tests
  12. Concomitant use of an MAOI (if receiving methylphenidate during this study), or use of an MAOI within the last 14 days prior to receiving methylphenidate.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02178995

Locations
United States, California
Stanford University
Palo Alto, California, United States, 94305
Sponsors and Collaborators
Kimford Jay Meador
Investigators
Study Director: Jesse M Adams, MD Stanford University
Principal Investigator: Kimford Meador, MD Stanford University
Study Chair: John Barry, MD Stanford University
  More Information

Responsible Party: Kimford Jay Meador, Professor, Stanford University
ClinicalTrials.gov Identifier: NCT02178995     History of Changes
Other Study ID Numbers: MPH in epilepsy 
Study First Received: June 24, 2014
Results First Received: June 4, 2016
Last Updated: July 19, 2016
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Epilepsy
Attention Deficit Disorder with Hyperactivity
Cognition Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Attention Deficit and Disruptive Behavior Disorders
Neurodevelopmental Disorders
Mental Disorders
Neurocognitive Disorders
Methylphenidate
Central Nervous System Stimulants
Physiological Effects of Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on December 02, 2016