E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 measure in vivo effect on neuroinflammation of treatment with celecoxib, a selective COX-2 inhibitor, in PD using PK111-95 and PET. Celecoxib showed broad utility in animal models of neurodegeneration. Neurochemical effect of the treatment on microglia activation in humans will be measured in vivo comparing the PET scans of 10 early stage PD patients before and after one month of treatment. Differences between the first and second scan will be compared to a first and second scan in a group of 10 PD patients without treatment with celecoxib, to compare test-retest variability.
This study is meant to be a pilot study which tries to deliver a proof of principle, namely whether neuroinflammation of the brain can be blocked by available medication and whether this can be monitored by the applied radiotracer scans. If a positive result is achieved then a larger study is warranted to investigate longitudinally whether long-term treatment has a positive clinical effect. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Age over 40 -Informed consent. -Regarded by the treating physician to have competence of judgement. -Compliance with the criteria for possible or probable PD as proposed by Gelb, Oliver and Gilman [1999] -early stage PD; Hoehn and Yahr stages 1-2.
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E.4 | Principal exclusion criteria |
- Prior cardiovascular brain disease, other brain disease (including former traumatic contusion) - Evidence of any significant general medical disease in medical history or at clinical exam; e.g. significant kidney or liver disease, evidence of autoimmune disease. - Evidence of psychiatric disease in medical history; e.g. depressive disorder, schizophrenia. - Use of anti-inflammatory medication: NSAID’s and steroids. - Use of benzodiazepines. Benzodiazepines have affinity for the PBR receptor that binds the PET tracer PK11195 and can interfere with the study. - Contra-indications for celecoxib use: active gastric ulcers or gastric bleeding. Asthma attack, urticaria, angio-edema after use of prostaglandine synthetase inhibitors. Inflammatory bowel disease. Moderate or severe liver or kidney disease. Severe heart failure. Allergy to sulphonamide. - Abnormalities at clinical neurological examination (other than PD) - Pregnancy in women of childbearing potential. - Exposure to a significant amount of radiation in the past year. - Radiological workers. |
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E.5 End points |
E.5.1 | Primary end point(s) |
[11C]-PK111-95 Binding Potential (BP) images will be generated based on a simplified reference tissue model4;13. Cluster analysis will be used to extract and identify a normal brain reference input function for individual PD cases. The reference tissue model will be compared to parametric analysis, using plasma input data and Logan analysis to generate distribution volume images. Pixel-by-pixel analysis will be done using Statistical Parametric Mapping program (SPM2)14. A coupled t-test will be applied to evaluate differences between the two scans. P-value of 0.001, uncorrected for multiple comparisons / 0.05 after correction will be taken for statistical significance. |
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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) | 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 | Information not present in EudraCT |
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 | Yes |
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 | Information not present in EudraCT |
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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End is after completion of the protocol in 20 patients. End of 2007 |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |