. 2020 Jan 6;21(1):14.

doi: 10.1186/s13063-019-3758-9.

Vitamin D supplementation compared to placebo in people with First Episode psychosis - Neuroprotection Design (DFEND): a protocol for a randomised, double-blind, placebo-controlled, parallel-group trial

Fiona Gaughran^{1

2}, Dominic Stringer³, Michael Berk⁴, Shubulade Smith^{5

6}, David Taylor⁶, Eromona Whiskey^{5

6}, Sabine Landau³, Robin Murray^{5

6}, Philip McGuire^{5

6}, Poonam Gardner-Sood^{5

6}, Gabriella Wojewodka⁵, Simone Ciufolini^{5

6}, Harriet Jordan⁵, Jessie Clarke⁵, Lauren Allen⁵, Amir Krivoy^{5

6}, Brendon Stubbs^{5

6}, Philippa Lowe⁷, Maurice Arbuthnott⁸, Shanaya Rathod⁹, Andrew Boardman¹⁰, Mudasir Firdosi¹¹, John J McGrath^{12

13

14}

Affiliations

¹ Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology and Neuroscience, 16 De Crespigny Park, London, SE5 8AF, UK. fiona.p.gaughran@kcl.ac.uk.
² South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, UK. fiona.p.gaughran@kcl.ac.uk.
³ Department of Biostatistics and Health Informatics, King's College London, Institute of Psychiatry, Psychology and Neuroscience, 16 De Crespigny Park, London, SE5 8AF, UK.
⁴ Deakin University and Barwon Health, Ryrie Street, Geelong, Victoria, 3220, Australia.
⁵ Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology and Neuroscience, 16 De Crespigny Park, London, SE5 8AF, UK.
⁶ South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, UK.
⁷ Carer Expert and Chair of Trustees, Rethink Mental Illness, 89 Albert Embankment, London, SE1 7TP, UK.
⁸ , London, UK.
⁹ Clinical Trials Facility, Research Department, Tom Rudd Unit, Moorgreen Hospital, Southampton, SO3 03J, UK.
¹⁰ Cheshire & Wirral Partnership NHS Trust, Churton House, Countess of Chester Health Park, Chester, CH2 1BQ, UK.
¹¹ South West London and St George's Mental Health NHS Trust, Queen Mary's Hospital, Roehampton Lane, London, SW15 5PN, UK.
¹² Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD, 4076, Australia.
¹³ Queensland Brain Institute, University of Queensland, Brisbane, QLD, 4072, Australia.
¹⁴ National Centre for Register-Based Research, Aarhus University, 8000, Aarhus C, Denmark.

PMID: 31907006
PMCID: PMC6945550
DOI: 10.1186/s13063-019-3758-9

Vitamin D supplementation compared to placebo in people with First Episode psychosis - Neuroprotection Design (DFEND): a protocol for a randomised, double-blind, placebo-controlled, parallel-group trial

Fiona Gaughran et al. Trials. 2020.

. 2020 Jan 6;21(1):14.

doi: 10.1186/s13063-019-3758-9.

Authors

Affiliations

¹ Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology and Neuroscience, 16 De Crespigny Park, London, SE5 8AF, UK. fiona.p.gaughran@kcl.ac.uk.
² South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, UK. fiona.p.gaughran@kcl.ac.uk.
³ Department of Biostatistics and Health Informatics, King's College London, Institute of Psychiatry, Psychology and Neuroscience, 16 De Crespigny Park, London, SE5 8AF, UK.
⁴ Deakin University and Barwon Health, Ryrie Street, Geelong, Victoria, 3220, Australia.
⁵ Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology and Neuroscience, 16 De Crespigny Park, London, SE5 8AF, UK.
⁶ South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, UK.
⁷ Carer Expert and Chair of Trustees, Rethink Mental Illness, 89 Albert Embankment, London, SE1 7TP, UK.
⁸ , London, UK.
⁹ Clinical Trials Facility, Research Department, Tom Rudd Unit, Moorgreen Hospital, Southampton, SO3 03J, UK.
¹⁰ Cheshire & Wirral Partnership NHS Trust, Churton House, Countess of Chester Health Park, Chester, CH2 1BQ, UK.
¹¹ South West London and St George's Mental Health NHS Trust, Queen Mary's Hospital, Roehampton Lane, London, SW15 5PN, UK.
¹² Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD, 4076, Australia.
¹³ Queensland Brain Institute, University of Queensland, Brisbane, QLD, 4072, Australia.
¹⁴ National Centre for Register-Based Research, Aarhus University, 8000, Aarhus C, Denmark.

PMID: 31907006
PMCID: PMC6945550
DOI: 10.1186/s13063-019-3758-9

Abstract

Background: People experiencing their first episode of psychosis are often deficient in vitamin D. Observational studies have reported an association between low vitamin D concentrations and poorer subsequent health outcomes in psychosis. A vitamin D deficiency in neonates and children has been linked to a later increased risk of schizophrenia and psychotic-like experiences. This trial aims to examine the effect of high-dose vitamin D supplementation on outcomes in early psychosis. We hypothesise that vitamin D supplementation will be associated with better mental health outcomes.

Methods/design: The DFEND study is a multicentre double-blind placebo-controlled parallel-group trial of vitamin D supplementation in people with early psychosis. Patients with an ICD-10 diagnosis of functional psychosis will be randomised in a 1:1 ratio to receive either 120,000 IU/month of vitamin D (cholecalciferol) or a matched placebo for 6 months. The primary outcome is the total Positive and Negative Syndrome Scale (PANSS) score at the 6-month follow-up for all patients. Secondary outcomes include assessment of mood (Calgary Depression Scale), general function (Global Assessment of Functioning), cardiovascular risk (body mass index, waist circumference, C-reactive protein, cholesterol and HbA1c) and vitamin D levels at the 6-month follow-up. Additionally, 3- and 6-month total PANSS scores will be analysed for those with inadequate vitamin D levels at the baseline.

Discussion: The DFEND study is the first trial to examine whether vitamin D supplementation in early psychosis is associated with better mental health outcomes. The findings of this study may help to resolve the clinical equipoise regarding the benefits and cost-effectiveness of routine vitamin D supplementation in people with psychosis.

Trial registration: ISRCTN, ISRCTN12424842. Registered on 25 February 2015.

Keywords: 25OHD; First episode; Mental health; Positive and Negative Syndrome Scale; Psychosis; Randomised controlled trial; Vitamin D.

PubMed Disclaimer

Conflict of interest statement

FG has received honoraria for advisory work and lectures, has received support for Continuing Medical Education (CME) activities in the last 3 years from Lundbeck, Otsaka and Sunovion, is a collaborator on an NHS Innovations project co-funded by Janssen and has a family member with professional links to Lilly and GSK, including shares. RM has received honoraria for lectures from Lundbeck, Janssen and Sunovion. SR has received honoraria for lectures from Lundbeck. All other authors declare that they have no competing interests.

Figures

**Fig. 1**
SPIRIT figure. Schedule of enrolment, interventions, and assessments in the DFEND Study. *Blood sampling for calcium levels (including a parathyroid hormone test if hypercalcaemic) will always be done at month 3 but can be done at all monthly visits if patient reports nausea or vomiting. NOS Nottingham Onset Schedule, PANSS Positive and Negative Syndrome Scale, GAF Global Assessment Functioning, CDS Calgary Depression Scale, OPCRIT Operational Criteria, IPAQ International Physical Activity Questionnaire, SIMPAQ Simple Physical Activity Questionnaire

See this image and copyright information in PMC

References

1. DeLuca GC, Kimball SM, Kolasinski J, Ramagopalan SV, Ebers GC. Review: the role of vitamin D in nervous system health and disease. Neuropathol Appl Neurobiol. 2013;39(5):458–484. doi: 10.1111/nan.12020. - DOI - PubMed
1. Wrzosek M, Lukaszkiewicz J, Wrzosek M, Jakubczyk A, Matsumoto H, Piatkiewicz P, et al. Vitamin D and the central nervous system. Pharmacol Rep. 2013;65(2):271–278. doi: 10.1016/S1734-1140(13)71003-X. - DOI - PubMed
1. McCann JC, Ames BN. Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction? FASEB J. 2008;22(4):982–1001. doi: 10.1096/fj.07-9326rev. - DOI - PubMed
1. Eyles DW, Burne TH, McGrath JJ. Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol. 2013;34(1):47–64. doi: 10.1016/j.yfrne.2012.07.001. - DOI - PubMed
1. Kesby JP, Turner KM, Alexander S, Eyles DW, McGrath JJ, Burne THJ. Developmental vitamin D deficiency alters multiple neurotransmitter systems in the neonatal rat brain. Int J Dev Neurosci. 2017;62:1–7. doi: 10.1016/j.ijdevneu.2017.07.002. - DOI - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

Grants and funding

13T-006/Stanley Medical Research Institute

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information
Research Materials
- NCI CPTC Antibody Characterization Program

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Vitamin D supplementation compared to placebo in people with First Episode psychosis - Neuroprotection Design (DFEND): a protocol for a randomised, double-blind, placebo-controlled, parallel-group trial

Affiliations

Vitamin D supplementation compared to placebo in people with First Episode psychosis - Neuroprotection Design (DFEND): a protocol for a randomised, double-blind, placebo-controlled, parallel-group trial

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials