NCT03814356

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

Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness - A Phase 1 Study

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: Massachusetts General Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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

Interventions

Type	Name	Description
DRUG	Methylphenidate	IV MPH

Timeline

• Start date: 2020-08-24
• Primary completion: 2024-04-01
• Completion: 2026-06-30
• First posted: 2019-01-24
• Last updated: 2025-10-29
• Results posted: 2025-10-29

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study