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

NCT03814356 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: 140675DP2HD101400
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Injury Traumatic Severe (Diagnosis); Coma; Consciousness, Level Altered; Anoxic Brain Injury

Outcome Measures

Primary Outcomes (1)

• 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

  4 Days

Secondary Outcomes (4)

• Time to Maximal Serum Concentration of IV Methylphenidate (MPH)

  4 Days

• Serum Half-life of IV Methylphenidate (MPH)

  4 Days

• Cerebral Cortical Connectivity as Measured by fMRI

  4 Days

• Cerebral Cortical Connectivity as Measured by EEG

  4 Days

Study Arms (1)

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.

Drug: Methylphenidate

Interventions

Methylphenidate DRUG

IV MPH

Also known as: MPH

IV MPH

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Severe, acute traumatic brain injury
• Diagnosis of Coma, Vegetative State, or Minimally Conscious State

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• 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.

  PMID: 32794142 BACKGROUND

Related Links

• Homepage of the Laboratory for NeuroImaging of Coma and Consciousness

MeSH Terms

Conditions

Disease; Coma; Consciousness Disorders; Hypoxia-Ischemia, Brain

Interventions

Methylphenidate; 5,10-dihydro-5-methylphenazine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Unconsciousness; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Brian L. Edlow, M.D.
• Organization: Massachusetts General Hospital

bedlow@mgh.harvard.edu

617-724-6352

Study Officials

• Brian L Edlow, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Laboratory for NeuroImaging of Coma and Consciousness (NICC)

Study Record Dates

• First Submitted: January 15, 2019
• First Posted: January 24, 2019
• Study Start: August 24, 2020
• Primary Completion: April 1, 2024
• Study Completion (Estimated): June 30, 2026
• Last Updated: October 29, 2025
• Results First Posted: October 29, 2025

Record last verified: 2025-10

Locations

US (1)