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

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ClinicalTrials.gov Identifier: NCT02015949
Recruitment Status : Completed
First Posted : December 19, 2013
Last Update Posted : January 10, 2017
Information provided by (Responsible Party):
Imperial College London

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Drug: Methylphenidate Drug: Placebo Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: The Control of Brain Networks After Traumatic Brain Injury: a Neuroimaging and Neuropsychological Study of Dopamine and Cognition
Study Start Date : February 2014
Primary Completion Date : January 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Methylphenidate
2 weeks of 0.3mg/kg twice daily of methylphenidate to the nearest 5mg
Drug: Methylphenidate
Cross-over design comparing methylphenidate 0.3 mg/kg (to nearest 5mg) twice daily to placebo
Placebo Comparator: Sugar pill
2 weeks of twice daily placebo
Drug: Placebo
Twice daily placebo tablet for two weeks

Primary Outcome Measures :
  1. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02015949

United Kingdom
Imperial College
London, United Kingdom
Sponsors and Collaborators
Imperial College London
Principal Investigator: David J Sharp Imperial College London

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT02015949     History of Changes
Other Study ID Numbers: 13HH1824
2013-004244-37 ( EudraCT Number )
First Posted: December 19, 2013    Key Record Dates
Last Update Posted: January 10, 2017
Last Verified: May 2016

Additional relevant MeSH terms:
Wounds and Injuries
Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Central Nervous System Stimulants
Physiological Effects of Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Cardiotonic Agents
Autonomic Agents
Peripheral Nervous System Agents
Protective Agents