E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cerebrospinal fluid circulation disorder seen in clinically suspected idiopathic normal pressure hydrocephalus |
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E.1.1.1 | Medical condition in easily understood language |
Brain water circulation disorder in patients with abnormally enlarged intracranial space |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 |
To quantify the distribution and rate of elimination of the contrast agent as assessed by repeated MRI in humans. We will also document any adverse avents related to the administration of Gadovist |
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E.2.2 | Secondary objectives of the trial |
To investigate the driving mechanism of the flow and if the quantified glymphatic function can be used to predict which INPH patients that will be improved by shunting with CSF shunt. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients investigated for suspected idiopathic normal pressure hydrocephalus at Umeå University Hospital |
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E.4 | Principal exclusion criteria |
Age < 65 Known contradicting allergies Known contraindications for magnetic resonance imaging Renal impairment (as deffined by blood test at admission) Current treatment with anticoagulation medication Low threshold to seizures History of bronchial asthma Previous investigation with gadolinium contrast medium Mini Mental State Examination (MMSE) <18 Not able to understand instructions needed for informed concent. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time-dependent change in signal intensity on brain MRI after intrathecal contrast administration will be analyzed with an indicator dilution algorithm that will be optimized using computational fluid dynamic simulations.
Registration of possible adverse events related to the intrathecal injection of Gadovist. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After the single intrathecal injection of the contrast agent, MRI will be done at approximatly 4 time-points within 24 hours post injection.
Advers events will be registered during the first 24h post injection and during follow up. |
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E.5.2 | Secondary end point(s) |
Comparison between the distribution of the contrast and other MRI-sequences and cerebrospinal fluid dynamic parameters which provides us with information regarding possible driving mechanisms for the distribution.
Quantified pre-operative glymphatic function will be correlated to clinical improvement after CSF shunting of INPH patients. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Cerebrospinal fluid dynamic data will be gathered in conjunction with the injection of the contrast agent. The other MRI-sequences will be done at the different time-points discribed in E.5.1.1 as well as in separate scans not involving an injection of a contrast agent.
Clinical improvement will be accessed 3 months after surgery.
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
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 | No |
E.8.2.3 | Other | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |