Problems With Morphine Use in Patients With a Severe Brain Injury

NCT00196131 | Unknown Phase 1

• 2 other identifiers: Dal05-01CIHRMOP-74451
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothesis: During severe brain trauma (injury, surgery) the ensuing inflammatory response in the central nervous system (CNS) results in a decrease in the expression of the transporter protein p-glycoprotein (PGP) in the blood brain barrier. This loss results in the penetration into the brain of certain drugs that are normally excluded by the transporter protein. In this study the working hypothesis is that the agitation observed in patients with CNS trauma treated with morphine is related to the inflammation evoked loss of PGP in the blood brain barrier and the accumulation of the morphine metabolite 3-morphine glucuronide.

Conditions

Head Trauma; Subarachnoid Hemorrhage; Close Head Injury

Keywords

morphine; head injury; SAH

Outcome Measures

Primary Outcomes (1)

• see the ratios of cerebrospinal fluid (CSF)/blood increase with time as the inflammation progresses

  prospective

Secondary Outcomes (1)

• ratios of morphine and its metabolites in CSF and blood with the RASS will determine if observed CNS stimulation occurs at a time when the levels of 3-morphine glucuronide is high on the brain side of the blood brain barrier

  prospective

Study Arms (1)

0

NO INTERVENTION

Drug: morphine

Interventions

morphine DRUG

only patients with a head injury currently receiving Morphine continuously or prm can and have an ICP drain can be enrolled into study

0

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Sustained a head trauma (closed head injury or subarachnoid hemorrhage \[SAH\])
• Fitted with a intraventricular drainage catheter
• Currently being treated with morphine

You may not qualify if:

• Patient is receiving another PGP inhibitor drug other than morphine or midazolam

Sponsors & Collaborators

• Dalhousie University: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Capital Health -QE II HSC

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Related Publications (1)

• Goralski KB, Hartmann G, Piquette-Miller M, Renton KW. Downregulation of mdr1a expression in the brain and liver during CNS inflammation alters the in vivo disposition of digoxin. Br J Pharmacol. 2003 May;139(1):35-48. doi: 10.1038/sj.bjp.0705227.

  PMID: 12746221 BACKGROUND

MeSH Terms

Conditions

Craniocerebral Trauma; Subarachnoid Hemorrhage; Head Injuries, Closed

Interventions

Morphine

Condition Hierarchy (Ancestors)

Trauma, Nervous System; Nervous System Diseases; Wounds and Injuries; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Wounds, Nonpenetrating

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Richard I Hall, MD

  Capital Health- QE II HSC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 20, 2005
• Study Start: January 1, 2005
• Study Completion: April 1, 2008
• Last Updated: April 10, 2008

Record last verified: 2006-09

Locations

CA (1)