Trial Outcomes & Findings for Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness (NCT NCT03814356)

Last Updated: 2025-10-29

Results Overview

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

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1

Target enrollment

10 participants

Primary outcome timeframe

4 Days

Results posted on

2025-10-29

Participant Flow

10 patients were enrolled with informed consent provided by surrogate decision-makers, but one patient was withdrawn from the study by surrogate decision-makers prior to any study procedures were performed.

Participant milestones

Participant milestones
Measure	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. Methylphenidate: IV MPH
Overall Study STARTED	9
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IV MPH n=9 Participants 9 patients with severe traumatic brain injury (TBI), age range 25-77, all male.
Age, Continuous	49.3 years STANDARD_DEVIATION 21.3 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 Days

Population: 9 participants received the 0.5 mg/kg IV MPH dose and and the 1.0 mg/kg IV MPH dose. 6 participants received the 2.0 mg/kg IV MPH dose.

Outcome measures

Outcome measures
Measure	IV MPH n=9 Participants All patients received IV Methylphenidate (MPH). Patients received 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) necessitated dose de-escalation or a serious adverse event (SAE) necessitated that the patient stop participation in the study.
Number of Participants With Adverse Events at Each Dose 1.0 mg/kg IV MPH	2 Participants
Number of Participants With Adverse Events at Each Dose 0.5 mg/kg IV MPH	0 Participants
Number of Participants With Adverse Events at Each Dose 2.0 mg/kg IV MPH	1 Participants

SECONDARY outcome

Timeframe: 4 Days

Population: We measured the median (range) time (hours) to maximum concentrations at 0.5, 1.0, and 2.0 mg/kg doses of IV MPH.

The median (range) time (hours) to maximum concentrations at 0.5, 1.0, and 2.0 mg/kg doses was measured.

Outcome measures

Outcome measures
Measure	IV MPH n=9 Participants All patients received IV Methylphenidate (MPH). Patients received 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) necessitated dose de-escalation or a serious adverse event (SAE) necessitated that the patient stop participation in the study.
Time to Maximal Serum Concentration of IV Methylphenidate (MPH) 0.5 mg/kg IV MPH	0.12 hours Interval 0.08 to 0.13
Time to Maximal Serum Concentration of IV Methylphenidate (MPH) 1.0 mg/kg IV MPH	0.15 hours Interval 0.07 to 0.18
Time to Maximal Serum Concentration of IV Methylphenidate (MPH) 2.0 mg/kg IV MPH	0.23 hours Interval 0.2 to 0.3

SECONDARY outcome

Timeframe: 4 Days

Population: The mean (SD) serum half-lives (hours) at 0.5, 1.0, and 2.0 mg/kg doses was assessed.

The mean (SD) serum half-lives (hours) at 0.5, 1.0, and 2.0 mg/kg doses was assessed.

Outcome measures

Outcome measures
Measure	IV MPH n=9 Participants All patients received IV Methylphenidate (MPH). Patients received 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) necessitated dose de-escalation or a serious adverse event (SAE) necessitated that the patient stop participation in the study.
Serum Half-life of IV Methylphenidate (MPH) 0.5 mg/kg	5.07 hours Standard Deviation 2.55
Serum Half-life of IV Methylphenidate (MPH) 1.0 mg/kg	4.39 hours Standard Deviation 1.92
Serum Half-life of IV Methylphenidate (MPH) 2.0 mg/kg	5.01 hours Standard Deviation 1.80

SECONDARY outcome

Timeframe: 4 Days

Population: Functional MRI data were obtained in two study participants.

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.

Outcome measures

Outcome measures
Measure	IV MPH n=2 Participants All patients received IV Methylphenidate (MPH). Patients received 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) necessitated dose de-escalation or a serious adverse event (SAE) necessitated that the patient stop participation in the study.
Cerebral Cortical Connectivity as Measured by fMRI	1 number of responders

SECONDARY outcome

Timeframe: 4 Days

Population: EEG data were obtained in all nine study participants at the 0.5 mg/kg dose and 1.0 mg/kg dose, and in 6 participants at the 2.0 mg/kg dose.

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.

Outcome measures

Outcome measures
Measure	IV MPH n=9 Participants All patients received IV Methylphenidate (MPH). Patients received 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) necessitated dose de-escalation or a serious adverse event (SAE) necessitated that the patient stop participation in the study.
Cerebral Cortical Connectivity as Measured by EEG 0.5 mg/kg IV MPH	4 number of responders
Cerebral Cortical Connectivity as Measured by EEG 1.0 mg/kg IV MPH	2 number of responders
Cerebral Cortical Connectivity as Measured by EEG 2.0 mg/kg IV MPH	0 number of responders

Adverse Events

0.5 mg/kg IV MPH

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

1.0 mg/kg IV MPH

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

2.0 mg/kg IV MPH

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	0.5 mg/kg IV MPH n=9 participants at risk 9 patients received 0.5 mg/kg IV MPH.	1.0 mg/kg IV MPH n=9 participants at risk 9 patients received 1.0 mg/kg IV MPH.	2.0 mg/kg IV MPH n=6 participants at risk 6 patients received 0.5 mg/kg IV MPH.
Nervous system disorders Paroxysmal Sympathetic Hyperactivity	0.00% 0/9 • 4 days	11.1% 1/9 • Number of events 1 • 4 days	0.00% 0/6 • 4 days
Nervous system disorders Insomnia	0.00% 0/9 • 4 days	11.1% 1/9 • Number of events 1 • 4 days	0.00% 0/6 • 4 days
Gastrointestinal disorders Emesis	0.00% 0/9 • 4 days	11.1% 1/9 • Number of events 1 • 4 days	0.00% 0/6 • 4 days
Hepatobiliary disorders Transaminitis (increased ALT/AST)	0.00% 0/9 • 4 days	0.00% 0/9 • 4 days	16.7% 1/6 • Number of events 1 • 4 days

Additional Information

Brian L. Edlow, M.D.

Massachusetts General Hospital

Phone: 617-724-6352

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place