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

NCT ID: NCT03814356

Last Updated: 2025-10-29

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-24
• Study Completion Date: 2026-06-30

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Methylphenidate

Intervention Type: DRUG

IV MPH

Interventions

Methylphenidate

IV MPH

Intervention Type: DRUG

Other Intervention Names

MPH

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years

2. Severe, acute traumatic brain injury

3. Diagnosis of Coma, Vegetative State, or Minimally Conscious State

Exclusion Criteria

1. Penetrating brain injury caused by a metallic missile/object (e.g. bullet)

2. Body metal contraindicating MRI

3. Prisoner or ward of the state

4. Neurological

1. Bilateral dilated unresponsive pupils

2. 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)

3. Intracranial bolt

4. Status epilepticus or concern for post-ictal state

5. Cardiovascular

1. Poorly controlled hypertension (SBP > 200 mmHg of DBP > 120mmHg for 30 minutes, despite anti-hypertensive therapy, within the past 24 hours)

2. Coronary artery disease

3. ST elevation myocardial infarction

4. Acute coronary syndrome

5. Hemodynamically significant dysrhythmia

6. Congestive heart failure

7. Cardiomyopathy (including Takotsubo cardiomyopathy)

8. Other severe structural cardiac abnormalities

6. Renal

a. Renal failure requiring renal replacement therapy (e.g. CVVH or HD)

7. Endocrine

a. History of or clinical suspicion for thyrotoxicosis

8. Reproductive

a. Pregnancy

9. Ophthalmologic

a. History of glaucoma

10. Pharmacologic

a. Monoamine oxidase inhibitor therapy within past 14 days

11. Other

1. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Brian L. Edlow, M.D.

Director, Laboratory for NeuroImaging of Coma and Consciousness (NICC)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brian L Edlow, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 32794142 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.comarecoverylab.org/

Homepage of the Laboratory for NeuroImaging of Coma and Consciousness

Other Identifiers

DP2HD101400

Identifier Type: NIH

Identifier Source: secondary_id

View Link

140675

Identifier Type: -

Identifier Source: org_study_id