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Trial record 33 of 39 for:    "Brain Injury" | "Dopamine"

Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness (STIMPACT)

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ClinicalTrials.gov Identifier: NCT03814356
Recruitment Status : Not yet recruiting
First Posted : January 24, 2019
Last Update Posted : March 21, 2019
Sponsor:
Information provided by (Responsible Party):
Brian L. Edlow, M.D., Massachusetts General Hospital

Brief Summary:
Phase 1 of the STIMPACT trial is an open label,dose-escalation,safety study of intravenous (IV) methylphenidate (MPH) therapy in patients with disorders of consciousness (DoC) caused by severe brain injuries. To be classified as having a DoC, a patient must be in a coma, vegetative state (VS), or minimally conscious state (MCS), as determined by behavioral assessment using the Coma Recovery Scale-Revised (CRS-R). Patients with DoC admitted to the intensive care unit (ICU) will be eligible for the study. A total of 10 patients with DoC will be enrolled in the Phase 1 study. Patients will receive escalating daily doses of IV MPH starting at 0.5 mg/kg, increasing stepwise to 1.0mg/kg and 2.0 mg/kg unless an adverse event (AE) necessitates dose de-escalation or a serious adverse event (SAE) necessitates that the patient stop participation in the study. Pharmacokinetics will be evaluated in selected patients with indwelling venous catheters or arterial catheters via serial serum measurements of MPH at each dose. The pharmacodynamic properties of IV MPH at each dose will be assessed by comparison of pre-versus post-dose EEG-based measures. The pharmacodynamic properties of the maximum tolerated dose will also be assessed by comparison of pre-versus post-dose resting state functional MRI (rs-fMRI) connectivity measures. Finally, we will test the association between structural connectivity of the ventral tegmental area (VTA), a dopaminergic brainstem nucleus that is believed to mediate MPH activation of the cerebral cortex, and EEG and rs-fMRI pharmacodynamic measures.

Condition or disease Intervention/treatment Phase
Brain Injury Traumatic Severe (Diagnosis) Coma Consciousness, Level Altered Anoxic Brain Injury Drug: Methylphenidate Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness - A Phase 1 Study
Estimated Study Start Date : April 1, 2019
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : March 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: IV MPH
All patients will receive IV Methylphenidate (MPH). Patients will receive escalating daily doses of IV MPH starting at 0.5 mg/kg, increasing stepwise to 1.0mg/kg and 2.0 mg/kg unless an adverse event (AE) necessitates dose de-escalation or a serious adverse event (SAE) necessitates that the patient stop participation in the study.
Drug: Methylphenidate
IV MPH
Other Name: MPH




Primary Outcome Measures :
  1. Adverse Events [ Time Frame: 4 Days ]
    The number of adverse events at each dose of IV MPH.

  2. Maximal Serum Concentration [ Time Frame: 4 Days ]
    The time to maximal serum concentration

  3. Serum Half-life [ Time Frame: 4 Days ]
    serum half-life of IV MPH at each dose


Secondary Outcome Measures :
  1. Cerebral Cortical Connectivity as Measured by EEG [ Time Frame: 4 Days ]
    The effect of each stimulant dose on cerebral cortical connectivity, as measured by EEG

  2. Cerebral Cortical Connectivity as Measured by fMRI [ Time Frame: 4 Days ]
    The effect of the maximum tolerated stimulant dose on brain connectivity as measured by resting state fMRI

  3. Correlation between Ventral Tegmental Area Hub Strength (as Measured by Diffusion MRI) and Resting State fMRI Responses to IV MPH [ Time Frame: 4 Days ]
    The structural connectivity of the ventral tegmental area within the ascending arousal network will correlate with resting state fMRI connectivity responses to IV MPH

  4. Correlation between the Ventral Tegmental Area Hub Strength (as Measured by Diffusion MRI), and EEG Responses to IV MPH [ Time Frame: 4 Days ]
    The structural connectivity of the ventral tegmental area within the ascending arousal network will correlate with EEG cerebral cortical connectivity responses to IV MPH



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Severe brain injury
  3. Diagnosis of Coma, Vegetative State, or Minimally Conscious State

Exclusion Criteria:

  1. Penetrating brain injury caused by a metallic missile/object (e.g. bullet)
  2. Body metal contraindicating MRI
  3. Prisoner or ward of the state
  4. Neurological a. Bilateral dilated unresponsive pupils b. Intracranial hypertension (Intracranial Pressure [ICP] > 20 cmH2O for > 5 min within past 24 hours with head of-bed at standard clinical angle of 30-45o) c. Intracranial bolt d. Status epilepticus or concern for post-ictal state
  5. Cardiovascular

    1. Poorly controlled hypertension (SBP sustained > 180 mmHg for 30 minutes, despite anti-hypertensive therapy, within the past 24 hours)
    2. Coronary artery disease
    3. Acute coronary syndrome Hemodynamically significant dysrhythmia
    4. Congestive heart failure
    5. Cardiomyopathy (including Takotsubo cardiomyopathy)
    6. Other severe structural cardiac abnormalities
  6. Renal

    a. Renal failure requiring renal replacement therapy (e.g. CVVH or HD)

  7. Endocrine a. Thyrotoxicosis
  8. Reproductive

    a. Pregnancy

  9. Ophthalmologic

    a. Glaucoma

  10. Pharmacologic a. Monoamine oxidase inhibitor therapy within past 14 days
  11. Other

    1. Any condition or finding that in the judgment of the PI or treating clinical team significantly increases the risk or significantly decreases the likelihood of a response to IV MPH

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03814356


Contacts
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Contact: Brian L Edlow, MD 6176433956 bedlow@mgh.harvard.edu
Contact: Yelena G Bodien, PhD ybodien@mgh.harvard.edu

Locations
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United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Brian L Edlow, MD    617-724-6352    bedlow@mgh.harvard.edu   
Contact: Yelena G Bodien, PhD    6176433956    ybodien@partners.org   
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
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Principal Investigator: Brian L Edlow, MD Massachusetts General Hospital

Additional Information:
Publications:
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Responsible Party: Brian L. Edlow, M.D., Director, Laboratory for NeuroImaging of Coma and Consciousness (NICC), Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT03814356     History of Changes
Other Study ID Numbers: 140675
First Posted: January 24, 2019    Key Record Dates
Last Update Posted: March 21, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Dopamine Uptake Inhibitors
Dopamine Agents
Consciousness Disorders
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Neurocognitive Disorders
Mental Disorders
Methylphenidate
Central Nervous System Stimulants
Physiological Effects of Drugs
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents