Vitamine D in Drug Resistant Epilepsy

• Status: Unknown status
• Trial end date: 2020-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Almost all patients with epilepsy living in the region of Paris have vitamin D deficiency, which is severe in 1/3 of the cases. The impact of this deficiency on epilepsy is unknown, despite the suggested benefits of vitamin D therapy including better seizure control and improvement of comorbidities (fatigue, anxiety, depression) in drug-resistant patients. Recommendations for vitamin D supplementation based on the serum level in the general population cannot be applied to patients with epilepsy due to interference of antiepileptic drugs in the vitamin D metabolism. Animal models, mechanisms of action studies and ecological information provide objective data for a direct antiepileptic effect of vitamin D. Human studies seem to confirm the antiepileptic effect of vitamin D but there are no controlled studies on large populations. The investigators aim to assess prospectively the effect of the treatment of vitamin D deficiency providing a high level of evidence. The investigators propose a multicentre placebo controlled randomized double-blind study, testing vitamin D supplementation against placebo in 400 drug-resistant patients to assess the short-term (3 months) and long-term (1 year) benefits on epilepsy. The investigators hypothesize that the treatment of vitamin D deficiency will result in significant reduction of seizure frequency, and improvement of comorbid symptoms as well as quality of life. The impact on the care of patients is important because better epilepsy control allows reduction of the antiepileptic drugs and side effects. This again is a key for the recovery of social and professional activities, and reduction of costs related to the disease.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre Hospitalier St Anne
• Collaborators: APHP; FFRE; LFCE
• Treatments: Cholecalciferol; Ergocalciferols; Vitamin D; Vitamins

Criteria

Inclusion Criteria:

• Age> 15 years

• Drug-resistant epilepsy (see definition above)

• Having at least 6 unprovoked seizures in the previous 3 months

• Epilepsy syndrome unequivocally established

• Ability to reliably quantify the seizure frequency

• Antiepileptic treatment stable for 3 months prior to inclusion

• No vitamin D treatment in the 6 months prior to inclusion vitamin D supplemental diet

• Medication compliance (confirmed by plasma levels if available)

• Agreeing to participate in the study

• Having a social insurance

• Parental agreement if patient below the age to be able to give consent (or guardian if protected adult)

Exclusion Criteria:

• Progressive brain pathology

• Status epilepticus in the 2 years prior to inclusion,

• epilepsy surgery planned in the current year

• Pregnancy or breast-feeding

• Treatments influencing the metabolism of vitamin D other than anticoagulants (rifamycin, isoniazid, ketoconazole, 5-FU fluorouracil), leucovorin)

• Known hypersensitivity to vitamin D, patients with a history of granulomatosis (especially sarcoidosis)

• Contraindication to treatment with Uvedose referring to the summary of product characteristics

• Current or past hypercalcemia or situations accompanied by increased vulnerability to hypercalcemia as arrhythmia or digitalis therapy, subjects with calcium lithiasis

• Moderate renal impairment with creatinine clearance <60 mL/mn assessed by MDRD (Modification of Diet in Renal Disease)

• Participation in other studies of other experimental drugs within 30 days before enrollment in the study

• Abuse of alcohol or drugs