Brain Injury Traumatic Severe (Diagnosis)Phase 1STIMPACTNCT03814356
Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness
A Phase 1 study testing Methylphenidate in people with Brain Injury Traumatic Severe (Diagnosis) and Coma, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Injury Traumatic Severe (Diagnosis), Coma, Consciousness, Level Altered
- What is being tested?
- Methylphenidate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Aug 2020to 30 Jun 2026
- Phase
- Phase 1
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Severe, acute traumatic brain injury
- Diagnosis of Coma, Vegetative State, or Minimally Conscious State
Who cannot join
- Penetrating brain injury caused by a metallic missile/object (e.g. bullet)
- Body metal contraindicating MRI
- Prisoner or ward of the state
- Neurological
- Bilateral dilated unresponsive pupils
- Intracranial hypertension (Intracranial Pressure [ICP] > 25 mmHg for > 5 min within past 24 hours with head-of-bed at standard clinical angle of 30-45 degrees)
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- Intracranial bolt
- Status epilepticus or concern for post-ictal state
- Cardiovascular
- Poorly controlled hypertension (SBP > 200 mmHg of DBP > 120mmHg for 30 minutes, despite anti-hypertensive therapy, within the past 24 hours)
- Coronary artery disease
- ST elevation myocardial infarction
- Acute coronary syndrome
- Hemodynamically significant dysrhythmia
- Congestive heart failure
- Cardiomyopathy (including Takotsubo cardiomyopathy)
- Other severe structural cardiac abnormalities
- Renal
- Renal failure requiring renal replacement therapy (e.g. CVVH or HD)
- Endocrine
- History of or clinical suspicion for thyrotoxicosis
- Reproductive
- Pregnancy
- Ophthalmologic
- History of glaucoma
- Pharmacologic
- Monoamine oxidase inhibitor therapy within past 14 days
- Other
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness - A Phase 1 Study
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.
Read the detailed description
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.
- Conditions
- Brain Injury Traumatic Severe (Diagnosis), Coma, Consciousness, Level Altered, Anoxic Brain Injury
- Being tested
- Methylphenidate
- Medical subject headings
- Disease, Coma, Consciousness Disorders, Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethylphenidateDrug
Also called MPH
IV MPH
| Study group | Role | What they receive |
|---|---|---|
| IV MPH | Experimental | 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. Receives: Drug: Methylphenidate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events at Each Dose
Adverse Events
An AE is defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related (21 CFR 312.32 (a)). In the STIMPACT Trial an AE may include, but is not limited to:
- Sustained hypertension = SBP > 200 mmHg or DBP > 120 mmHg for > 30 min, refractory to medical therapy, or
- Sustained tachycardia = HR > 120 bpm for > 30 min, refractory to medical therapy, or
- Sustained intracranial hypertension = ICP > 25 mmHg for > 5 min, refractory to medical therapy
Serious Adverse Events
An AE or suspected adverse reaction is considered "serious" if, in the view of the investigator or the Independent Medical Monitor, it results in any of the following outcomes:
- Death not related to withdrawal of life-sustaining therapy
- A life-threatening event
- Prolongation of existing hospitalization
- Significant incapacity or substantial disruption of the ability to conduct normal life function
Measured: 4 Days
Secondary outcomes (4)
Time to Maximal Serum Concentration of IV Methylphenidate (MPH)
The median (range) time (hours) to maximum concentrations at 0.5, 1.0, and 2.0 mg/kg doses was measured.
Measured: 4 Days
Serum Half-life of IV Methylphenidate (MPH)
The mean (SD) serum half-lives (hours) at 0.5, 1.0, and 2.0 mg/kg doses was assessed.
Measured: 4 Days
Cerebral Cortical Connectivity as Measured by fMRI
We performed a change-point analysis of time-series resting-state fMRI data to determine if individual participants responded to the 2.0 mg/kg dose of IV MPH. Specifically, we measured resting-state fMRI connectivity between the brainstem ventral tegmental area and the default mode network after the bolus of IV MPH as compared to before the bolus of IV MPH. The bolus of IV MPH was administered in the MRI scanner while the patient was undergoing a 40-minute resting-state fMRI (10 minutes of data acquisition pre-bolus, 30 minutes of data acquisition post-bolus). The goal of the analysis was to determine if each patient responded to IV MPH, as defined by a positive change point (i.e., increase in connectivity after the bolus of IV MPH). Connectivity was measured via Pearson correlations using the software package CONN.
Measured: 4 Days
Cerebral Cortical Connectivity as Measured by EEG
We performed a change-point analysis of time-series resting-state EEG data to determine if individual participants responded to each dose of IV MPH. Specifically, we measured resting-state EEG background rhythm, using the alpha/delta ratio as a quantitative biomarker of overall brain function (i.e., alpha/delta ratio was measured for all EEG leads in a clinical 19-electrode montage). In a continuous time-series analysis of resting EEG data acquired 1 hour before and 1 hour after each IV MPH bolus, we tested for a "change-point" in the alpha/delta ratio, which represents a statistically significant increase in alpha/delta ratio. The goal of the analysis was to determine if each patient responded to IV MPH, as defined by a positive change point (i.e., increase in alpha/delta after the bolus of IV MPH). EEG analyses were performed using MATLAB software.
Measured: 4 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2019
- Study start24 Aug 2020
- Primary completion1 Apr 2024
- Study completion30 Jun 2026 (estimated)
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 Brain Injury Traumatic Severe (Diagnosis)Studies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Brian L. Edlow, M.D., Massachusetts General Hospital
- Investigators
- Brian L Edlow, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03814356
- Sponsor's protocol ID
- 140675
- Other IDs
- DP2HD101400
- Acronym
- STIMPACT
- Status last verified
- Oct 2025
- First submitted
- 15 Jan 2019
- Last updated
- 29 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Edlow BL, Barra ME, Zhou DW, Foulkes AS, Snider SB, Threlkeld ZD, Chakravarty S, Kirsch JE, Chan ST, Meisler SL, Bleck TP, Fins JJ, Giacino JT, Hochberg LR, Solt K, Brown EN, Bodien YG. Personalized Connectome Mapping to Guide Targeted Therapy and Promote Recovery of Consciousness in the Intensive Care Unit. Neurocrit Care. 2020 Oct;33(2):364-375. doi: 10.1007/s12028-020-01062-7. Epub 2020 Aug 13.
PubMed 32794142