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Vitamine D in Drug Resistant Epilepsy (EPI-D)

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ClinicalTrials.gov Identifier: NCT03475225
Recruitment Status : Not yet recruiting
First Posted : March 23, 2018
Last Update Posted : April 13, 2018
Sponsor:
Collaborators:
APHP
FFRE
LFCE
Information provided by (Responsible Party):
Centre Hospitalier St Anne

Brief 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.

Condition or disease Intervention/treatment Phase
Drug Resistant Epilepsy Drug: Cholecalciferol Drug: Placebo Oral Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double blind
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double blind
Primary Purpose: Treatment
Official Title: Effect of the Treatment of Vitamin D Deficiency in Drug-resistant Epilepsy
Estimated Study Start Date : April 2018
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental Arm
Drug resistant epilepsy patients with proved Vitamin D deficiency (Serum vitamin D level <30ng/ml) Cholecalciferol. 5 doses of cholecalciferol (100 000 IU) in 3 months than 1 dose of cholecalciferol (100 000 IU) per month during 6 months
Drug: Cholecalciferol
Cholecalciferol delivery

Placebo Comparator: Control Arm
Drug resistant epilepsy patients with proved Vitamin D deficiency (Serum vitamin D level<30ng/ml) Placebo than cholecalciferol. 5 doses of placebo in 3 months than 5 doses of cholecalciferol (100 000 IU) in 3 months than 1 dose of cholecalciferol (100 000 IU) per month during 3 months.
Drug: Placebo Oral
manufactured to mimic Cholecalciferol




Primary Outcome Measures :
  1. Percentage reduction of the seizure frequency [ Time Frame: After 3 months of treatment of vitamin D deficiency ]
    With respect to the reference period


Secondary Outcome Measures :
  1. Effect on Fatigue scores : Modified Fatigue Impact Scale (M-FIS) [ Time Frame: 3, 6 and 12 months ]
    Total score at baseline and after Vitamin D treatment (range 0-200; higher values=worse outcome)

  2. Effect anxiety-depression : Hospital anxiety depression scale (HAD) [ Time Frame: 3, 6 and 12 months ]
    Total score at baseline and after Vitamin D treatment (range 0-42; higher values=worse outcome)

  3. Quality of Life in Epilepsy: (QOLIE 31) including 7 subscores: global score calculated on the basis on the mean of each subscore [ Time Frame: 3, 6 and 12 months ]
    Global score at baseline and after Vitamin D treatment (the higher score, the better outcome)

  4. Relationship between serum vitamin D levels and seizure frequency reduction after vitamin D treatment [ Time Frame: 3, 6 and 12 months ]
    Vitamin D levels and percentage reduction in the seizure frequency compared to the reference period

  5. Relationship between serum vitamin D levels and seizure frequency reduction after vitamin D treatment [ Time Frame: 3, 6 and 12 months. ]
    Vitamin D level and type of AED (enzyme inducer versus non enzyme inducer drugs)

  6. Relationship between serum vitamin D level and the type and dosage of antiepileptic drugs (AED) [ Time Frame: Baseline ]
    Vitamin D level and dose of AED (low dose versus high dose of enzyme inducer drugs)

  7. Responder rate [ Time Frame: 3, 6 and 12 months. ]
    Responder rate after Vitamin D treatment. Percentage of patients having a reduction of at least 50% of the seizure frequency

  8. Remission rate after Vitamin D treatment [ Time Frame: 3, 6 and 12 months.] ]
    Percentage of patients without any seizure (seizure freedom)

  9. Effect of Vitamin D according to epilepsy type [ Time Frame: 3, 6 and 12 months ]
    Responder rate in focal and generalized epilepsy

  10. Effect of Vitamin D according to epilepsy severity [ Time Frame: 3, 6 and 12 months ]
    Percentage of reduction of secondary generalized seizures and epileptic falls in respect to the reference period



Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03475225


Contacts
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Contact: CHASSOUX Francine, MD 145658226 ext +33 f.chassoux@ch-sainte-anne.fr

Sponsors and Collaborators
Centre Hospitalier St Anne
APHP
FFRE
LFCE
Investigators
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Principal Investigator: CHASSOUX Francine, MD Centre Hospitalier Sainte-Anne - 1, rue Cabanis 75014 Paris FRANCE

Publications:

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Responsible Party: Centre Hospitalier St Anne
ClinicalTrials.gov Identifier: NCT03475225     History of Changes
Other Study ID Numbers: D16-P15
First Posted: March 23, 2018    Key Record Dates
Last Update Posted: April 13, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centre Hospitalier St Anne:
Epilepsy
Drug-resistance
Vitamin D deficiency
Metabolism
Controlled study antiepileptic drugs
Additional relevant MeSH terms:
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Epilepsy
Drug Resistant Epilepsy
Vitamin D Deficiency
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Vitamin D
Ergocalciferols
Cholecalciferol
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents