Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness
Status:
Recruiting
Trial end date:
2023-02-23
Target enrollment:
Participant gender:
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.