E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with cerebral infarction or transient ischemic attack. |
Patienter med cerebralt infarkt, eller transitorisk iskæmisk attak. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with ischemic stroke or transient ischemic stroke. |
Patients med blodprop i hjernen eller forbigående blodprop i hjernen. |
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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 |
The purpose of this study is to investigate whether simvastatin in 3 different doses can cause peripheral neuropathy after 6 months of treatment assessed by nerve conduction, quantitative sensory testing and quantification of nerve fiber density in the dermo-epidermal transition. |
Formålet med studiet er at undersøge om simvastatin i 3 forskellige doser kan give perifer neuropati efter 6 måneders behandling bedømt ved nerveledning, kvantitativ sensorisk testning og kvantitering af nervefibertæthed i den dermo-epidermale overgang. |
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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 |
- Admitted to Odense University Hospital at the Department of Neurology or the Common Emergency Department at Neurology level. - Age: 40-80 years. - Newly diagnosed cerebral infarction or transient ischemic attack from clinical point of view and / or CT / MRI verification. For the treatment group applies: - In relation to the infarction the patients are in need of preventive statin therapy according to the guidelines of the department. For the control group applies: - In relation to the infarction the patients are not in need of preventive statin therapy according to the guidelines of the department or the patient does not want treatment. |
- Indlagt på Odense Universitetshospitals Neurologisk Afdeling eller hospitalets Fælles Akut Modtagelse i Neurologisk regi. - Alder: 40-80 år. - Nydiagnosticeret cerebralt infarkt eller TIA ud fra sikker klinik og/eller CT/MR-verifikation. For behandlingsgruppen gælder: - I relation til infarktet vurderes patienten at have behov for forebyggende statinbehandling ud fra afdelingens instruks. For kontrolgruppen gælder: - I relation til infarktet vurderes patienten ikke at have behov for forebyggende statinbehandling ud fra afdelingens instruks eller patienten ønsker ikke behandlingen. |
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E.4 | Principal exclusion criteria |
- Previous or current treatment with statins ( simvastatin , atorvastatin, rosuvastatin , fluvastatin , lovastatin and pravastatin ) . - Contraindications against statin therapy . - Current or previous treatment with drugs with known neurotoxic effects. - Current or previous co-morbidities that may cause polyneuropathy such as diabetes mellitus , cancer, disease , AIDP , CIDP , connective tissue diseases (ex. Sjogren 's syndrome, SLE , etc. . ), Vitamin B12 deficiency , hypothyroidism, myelomatosis , alcohol overuse (> 21 units for men and 14 units for women respectively per week ) , etc. . Furthermore patients who are being investigated for the same are being excluded. - Pre-existing peripheral neuropathy diagnose or symptoms suggestive of peripheral neuropathy - Patients with hypertriglyceridemia (> 10 mmol / l) . - Bilateral symptomatic cerebral infarcts , where one or both extremities are involved bilaterally , or other neurological disease which obviously will lead to sources of error in assessment with neuropathy rating scales. - High NIHSS if it is expected to result in a lasting , severe functional impact. - Aphasia , which makes an adequate information base for consent impossible. - Other neuropsychological sequelae than aphasia that makes the patient incapable of understanding the given information sufficiently. |
- Tidligere eller aktuel behandling med statiner (simvastatin, atorvastatin, rosuvastatin, fluvastatin, lovastatin og pravastatin). - Kontraindikationer mod statinbehandling. - Aktuel eller tidligere behandling med lægemidler med kendt neurotoksisk effekt. - Aktuel eller tidligere co-morbiditeter, der kan give polyneuropati så som diabetes mellitus, cancer sygdom, AIDP, CIDP, bindevævssygdomme (ex. Sjøgren syndrom, SLE mv.), vitamin B12-mangel, hypothyroidisme, myelomatose, kendt alkoholoverforbrug (> hhv. 21 genstande for mænd og 14 genstande for kvinder ugentligt) mv. Desuden eksluderes patienter, der er under udredning for samme. - Kendt diagnose med perifer neuropati eller i forvejen bestående symptomer tydende på perifer neuropati. - Patienter med hypertriglyceridæmi (>10 mmol/l). - Bilaterale symptomatiske cerebrale infarkter, hvor en eller begge ekstremiteter er involverede bilateralt, eller anden neurologisk sygdom, der åbenlyst vil medføre fejlkilder ved vurdering med benyttede neuropati-ratingsskalaer. - Høj NIHSS såfremt, det forventes at medføre en varig, svær funktionspåvirkning. - Afasi, der umuliggører et tilstrækkelig informationsgrundlag for samtykke. - Andre neuropsykologiske sequelae end afasi, der gør, at patienten vurderes ikke at kunne forstå den givne information i tilstrækkelig grad. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable will be nerve fiber density and nerve conduction assessed by the amplitude of the sensory action potential and conduction velocity in the sural nerve, amplitude of motor action potential and conduction velocity of the peroneal nerve and minimal F-wave latency in the tibial nerve. |
De primære effektvariable vil være nervefibertæthed samt nerveledning vurderet ved amplitude af sensorisk aktionspotentiale og ledningshastighed i n. suralis, amplitude af motorisk aktionspotentiale og ledningshastighed i n. peroneus, samt minimal F-wave latens i n. tibialis. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessments are made before and after 6 months of treatment. |
Der måles før og efter 6 måneders behandling. |
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E.5.2 | Secondary end point(s) |
Other variables are secondary. |
Øvrige variable betragtes som sekundære. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Assessments are made before and after 6 months of treatment. |
Der måles før og efter 6 måneders behandling. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
The aim is to investigate whether simvastatin can cause peripheral neuropathy as a side effect. |
Formålet er at undersøge om simvastatin kan give perifer neuropati som bivirkning. |
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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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Forskellige dosis-niveauer. |
Different dose levels. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Forskellige dosis-niveuaer + "Kontrolgruppen" får ikke nogen behandling. |
Diffenrent dose levels + The "control group" does not receive any treatment. |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 trial will end when 45 patients in each group (including the control group) has completed. |
Forsøget vil afsluttes, når 45 patienter i hver gruppe (inklusiv kontrolgruppen) har gennemført. |
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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 | 0 |