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A Phase 1 Study of Oral Vitamin D3 in Boys and Young Men With X-Linked Adrenoleukodystrophy.
Van Haren, Keith P; Cunanan, Kristen; Awani, Avni; Gu, Meng; Peña, Dalia; Chromik, Lindsay C; Povazan, Michal; Rossi, Nicole C; Goodman, Jordan; Sundaram, Vandana; Winterbottom, Jennifer; Raymond, Gerald V; Cowan, Tina; Enns, Gregory M; Waubant, Emmanuelle; Steinman, Lawrence; Barker, Peter B; Spielman, Daniel; Fatemi, Ali.
Affiliation
  • Van Haren KP; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Cunanan K; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Awani A; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Gu M; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Peña D; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Chromik LC; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Povazan M; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Rossi NC; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Goodman J; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Sundaram V; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Winterbottom J; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Raymond GV; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Cowan T; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Enns GM; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Waubant E; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Steinman L; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Barker PB; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Spielman D; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
  • Fatemi A; Department of Neurology (K.P.V.H., A.A., D.P., L.C.C., N.C.R., J.W., L.S.), Department of Pediatrics (K.P.V.H., T.C., G.M.E., L.S.), Quantitative Sciences Unit (K.C., V.S.) and Department of Radiology (M.G., D.S.), Stanford University School of Medicine Palo Alto, CA; Russell H. Morgan Department of
Neurol Genet ; 9(2): e200061, 2023 Apr.
Article in En | MEDLINE | ID: mdl-37090939
ABSTRACT
Background and

Objectives:

There are no therapies for preventing cerebral demyelination in X-linked adrenoleukodystrophy (ALD). Higher plasma vitamin D levels have been linked to lower risk of inflammatory brain lesions. We assessed the safety and pharmacokinetics of oral vitamin D dosing regimens in boys and young men with ALD.

Methods:

In this open-label, multicenter, phase 1 study, we recruited boys and young men with ALD without brain lesions to a 12-month study of daily oral vitamin D3 supplementation. Our primary outcome was attainment of plasma 25-hydroxyvitamin D levels in target range (40-80 ng/mL) at 6 and 12 months. Secondary outcomes included safety and glutathione levels in the brain, measured with magnetic resonance spectroscopy, and blood, measured via mass spectrometry. Participants were initially assigned to a fixed dosing regimen starting at 2,000 IU daily, regardless of weight. After a midstudy safety assessment, we modified the dosing regimen, so all subsequent participants were assigned to a weight-stratified dosing regimen starting as low as 1,000 IU daily.

Results:

Between October 2016 and June 2019, we enrolled 21 participants (n = 12, fixed-dose regimen; n = 9, weight-stratified regimen) with a median age of 6.7 years (range 1.9-22 years) and median weight of 20 kg (range 11.7-85.5 kg). The number of participants achieving target vitamin D levels was similar in both groups at 6 months (fixed dose 92%; weight stratified 78%) and 12 months (fixed dose 67%; weight stratified 67%). Among the 12 participants in the fixed-dose regimen, half had asymptomatic elevations in either urine calciumcreatinine or plasma 25-hydroxyvitamin D; no laboratory deviations occurred with the weight-stratified regimen. Glutathione levels in the brain, but not the blood, increased significantly between baseline and 12 months.

Discussion:

Our vitamin D dosing regimens were well tolerated and achieved target 25-hydroxyvitamin D levels in most participants. Brain glutathione levels warrant further study as a biomarker for vitamin D and ALD. Classification of Evidence This study provides Class IV evidence that fixed or weight-stratified vitamin D supplementation achieved target levels of 25-hydroxyvitamin D in boys and young men with X-ALD without brain lesions.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Clinical_trials Language: En Journal: Neurol Genet Year: 2023 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Clinical_trials Language: En Journal: Neurol Genet Year: 2023 Document type: Article