E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060690 |
E.1.2 | Term | Traumatic brain injury |
E.1.2 | System Organ Class | 100000004863 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To investigate the relationship between dopamine levels (a chemical in the brain which modulates brain functions) in the brain and its impact on cognition in patients who have suffered a traumatic brain injury. |
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E.2.2 | Secondary objectives of the trial |
2. To measure Dopamine Transporter levels (a molecule involved in controlling dopamine levels) following traumatic brain injury.
3. To test whether reduced dopamine levels after traumatic brain injury are correlated with abnormalities of brain functioning.
4. To investigate whether altered dopamine levels in the brain following traumatic brain injury are due to structural damage to particular parts of the dopamine system.
5. To test whether imaging techniques (MRI and/or SPECT scans) can be used to predict whether patients will respond to methylphenidate (a drug which increases dopamine levels).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria (TBI patients): • a diagnosis of traumatic brain injury (TBI) at least 3 months prior to recruitment into the study • age between 20 and 65 years • right-handed • capable of giving written informed consent • the presence of cognitive impairment as assessed on tests of information processing speed, working memory and attention tasks
Inclusion criteria (controls): • age between 20 and 65 years and in good general health (defined as no clinically relevant abnormalities identified on detailed medical history, physical examination, including blood pressure and pulse rate, and clinical laboratory tests) • right-handed • capable of giving written informed consent
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E.4 | Principal exclusion criteria |
Exclusion criteria (TBI patients): • 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
Exclusion criteria (controls): • unwillingness or inability to follow the procedures required • significant current or previously diagnosed neurological or psychiatric illness • 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Patients with low volume of distribution (VT) of the dopamine transporter (DAT) in the striatum will show significant improvement in the choice reaction time (CRT) task with methylphenidate. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
On completion of the 4 week drug trial and associated neuropsychological assessments. |
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E.5.2 | Secondary end point(s) |
• SPECT scan assessment of striatal dopamine levels • Diffusion MRI measures of white matter tract structure • Function of large scale intrinsic connectivity networks • Neuropsychological assessment of memory, information processing speed, attention and executive function
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Quality of single subject data will be assessed throughout the trial and group level analyses will be performed once the trial is completed
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial will be defined as the end of all trial procedures by the participants. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 1 |