Vitamin D deficiency and effect of treatment on seizure frequency and quality of life parameters in patients with drug-resistant epilepsy: A randomized clinical trial.
Study Goal
The researchers aimed to assess the effect of vitamin D3 supplementation on seizure frequency and quality of life in patients with drug-resistant epilepsy.
Results Summary
The study found no significant difference in seizure frequency reduction after 3 months of blinded treatment, but long-term supplementation (12 months) showed a 30% median reduction in seizures, improved fatigue, and quality of life. Bilateral tonic-clonic seizures were reduced by 52%.
Population
Patients aged ≥15 years with drug-resistant focal or generalized epilepsy and vitamin D deficiency (25(OH)D <30 ng/mL).
Effective Dosage
100,000 IU of vitamin D3 (five doses in 3 months, then 100,000 IU/month for 6 months).
Duration
12 months (3-month blinded period, followed by 9-month open-label period).
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
vitamin D3 (cholecalciferol, 100,000 IU, five doses in 3 months) | no change | seizure frequency reduction | patients aged ≥15 years with drug-resistant focal or generalized epilepsy and 25-hydroxyvitamin D < 30 ng/mL | - | did not significantly differ | #1 |
vitamin D3 supplementation | decrease | seizure frequency | patients aged ≥15 years with drug-resistant focal or generalized epilepsy and 25-hydroxyvitamin D < 30 ng/mL | 30% median reduction | significantly decreased | #2 |
vitamin D3 supplementation | decrease | bilateral tonic-clonic seizures | patients aged ≥15 years with drug-resistant focal or generalized epilepsy and 25-hydroxyvitamin D < 30 ng/mL | 52% | reduced | #3 |
vitamin D3 supplementation | increase | Modified Fatigue Impact Scale scores | patients aged ≥15 years with drug-resistant focal or generalized epilepsy and 25-hydroxyvitamin D < 30 ng/mL | - | significantly improved | #4 |
vitamin D3 supplementation | increase | Quality of Life in Epilepsy (QOLIE-31) scores | patients aged ≥15 years with drug-resistant focal or generalized epilepsy and 25-hydroxyvitamin D < 30 ng/mL | - | significantly improved | #5 |
vitamin D3 supplementation | decrease | seizure frequency reduction | patients aged ≥15 years with drug-resistant focal or generalized epilepsy and 25-hydroxyvitamin D < 30 ng/mL | - | correlated with | #6 |
OBJECTIVE: This study was undertaken to assess the effect of treatment of vitamin D deficiency in drug-resistant epilepsy. METHODS: We conducted a multicenter, double-blind, placebo-controlled, randomized clinical trial, including patients aged ≥15 years with drug-resistant focal or generalized epilepsy. Patients with 25-hydroxyvitamin D (25[OH]D) < 30 ng/mL were randomized to an experimental group (EG) receiving vitamin D3 (cholecalciferol, 100 000 IU, five doses in 3 months) or a control group (CG) receiving matched placebo. During the open-label study, EG patients received 100 000 IU/month for 6 months, whereas CG patients received five doses in 3 months then 1/month for 3 months. Monitoring included seizure frequency (SF), 25(OH)D, calcium, albumin, creatinine assays, and standardized scales for fatigue, anxiety-depression, and quality of life (Modified Fatigue Impact Scale [M-FIS], Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy [QOLIE-31]) at 3, 6, and 12 months. The primary efficacy outcome was the percentage of SF reduction compared to the reference period and CG at 3 months. Secondary outcomes were SF and bilateral tonic-clonic seizure (BTCS) reduction, scale score changes, and correlations with 25(OH)D during the follow-up. RESULTS: Eighty-eight patients were enrolled in the study (56 females, aged 17-74 years), with median baseline SF per 3 months = 16.5 and ≥2 antiseizure medications in 88.6%. In 75 patients (85%), 25(OH)D was <30 ng/mL; 40 of them were randomly assigned to EG and 34 to CG. After the 3-month blinded period, SF reduction did not significantly differ between groups. However, during the open-label period, SF significantly decreased (30% median SF reduction, 33% responder rate at 12 months). BTCSs were reduced by 52%. M-FIS and QOLIE-31 scores were significantly improved at the whole group level. SF reduction correlated with 25(OH)D > 30 ng/mL for >6 months. SIGNIFICANCE: Despite no proven effect after the 3-month blinded period, the open-label study suggests that long-term vitamin D3 supplementation with optimal 25(OH)D may reduce SF and BTCSs, with a positive effect on fatigue and quality of life. These findings need to be confirmed by further long-term studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03475225 (03-22-2018).