The Relationship Between Traumatic Brain Injury and Dopamine (a Chemical in the Brain)

Traumatic brain injury (TBI) is the most common cause of death and disability in young adults. Patients can experience significant problems with concentration, attention, and memory (so called 'cognitive impairments') following TBI. These cognitive impairments can drastically impact on a patient's well-being, and can lead to significant economic and social consequences. Roughly a quarter of TBI patients improve but an equal number deteriorate over time. The investigators know little about why patients vary so much in how they recover. Crucially, the investigators have no treatments to improve brain functioning or recovery after TBI.

Trials investigating ways of protecting the brain just after injury have been disappointing. An alternative strategy, however, is to improve the function of brain regions that remain intact, but that function inefficiently after TBI. The investigators know that dopamine (a chemical in the brain) is known to influence many brain functions and the investigators know that pathways in the brain that use dopamine are affected by TBI.

In humans, drugs that increase dopamine in the brain, such as methylphenidate, are sometimes used to enhance cognitive function after TBI, but the response to treatment can be highly variable between patients. Therefore, what is needed in the clinic is a way to target the use of these drugs to patients who are likely to respond.

In a single centre study, the investigators will use SPECT (Single Photon Emission Tomography) imaging to measure dopamine levels in the brain. MRI (Magnetic Resonance Imaging) scans will assess brain structure and function. The investigators will test whether treatment with methylphenidate improves cognitive functions in TBI patients who have ongoing cognitive problems, whether the mechanism involves a normalisation of brain functioning and whether brain dopamine levels can predict the magnitude of any improvement in symptoms.

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Key information

Conditions

Traumatic Brain Injury Brain Diseases Brain Injuries Brain Injuries, Traumatic Central Nervous System Diseases Craniocerebral Trauma Nervous System Diseases Trauma, Nervous System Wounds and Injuries

Age range

20 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Imperial College

London, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

a diagnosis of a moderate-severe traumatic brain injury (as defined by the Mayo TBI severity classification system) at least 3 months prior to recruitment into the study
age between 20 and 65 years
capable of giving written informed consent subjective complaint of cognitive difficulties by the participant, treating clinician, or caregiver

Exclusion criteria

unwillingness or inability to follow the procedures required
significant neurological or psychiatric illness diagnosed prior to the TBI
family history of a first degree relative with a psychotic illness
currently participating in a clinical trial or has done so within 1 month before screening
use of any medication or substance that, in the opinion of the investigators, would interfere with the study or compromise participant safety
history of a drug or other allergy that, in the opinion of the investigators, contraindicates their participation in the study
history of current or past drug or alcohol addiction
female participants who are breast feeding or pregnant (positive pregnancy test) or plan to become pregnant during the study
positive urine drug screen
contraindication to MRI scanning, assessed by a standard pre-MRI questionnaire
contraindication to the use of methylphenidate (including medications deemed to have a potentially serious interaction with methylphenidate as per the British National Formulary)
clinical evidence of motor symptoms of Parkinsonism as assessed by a Neurologist

Treatment and study plan

Methylphenidate

Drug

Cross-over design comparing methylphenidate 0.3 mg/kg (to nearest 5mg) twice daily to placebo

Placebo

Drug

Twice daily placebo tablet for two weeks

Primary outcomes

The change in Choice Reaction Time task with methylphenidate treatment in patients and its relationship to specific binding ratio (SBR) of the dopamine transporter (DAT) in the striatum.

Time frame: On completion of the four week drug trial phase

Sponsors and collaborators

Lead sponsor

Imperial College London

Other

Registry information

Official study title

The Control of Brain Networks After Traumatic Brain Injury: a Neuroimaging and Neuropsychological Study of Dopamine and Cognition

Important dates

Study start: 2014
Primary completion: 2017
First posted: Dec 19, 2013
Registry last updated: Jan 10, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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