Feasibility of 3-month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment: protocol for a randomised, placebo-controlled study

Introduction Melatonin has multiple proposed therapeutic benefits including antioxidant properties, synchronisation of the circadian system and lowering of blood pressure. In this protocol, we outline a randomised controlled trial to assess the feasibility, acceptability and tolerability of higher d...

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Main Authors: Craig L Phillips, Sharon L Naismith, Ronald R Grunstein, Bandana Saini, Christopher J Gordon, Nathaniel S Marshall, Camilla M Hoyos, Zoe Menczel Schrire, Shantel L Duffy, Loren Mowszowski, Haley M La Monica, Julia L Chapman, Simon J G Lewis
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Language:English
Published: BMJ Publishing Group 2021-02-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/11/2/e041500.full
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author Craig L Phillips
Sharon L Naismith
Ronald R Grunstein
Bandana Saini
Christopher J Gordon
Nathaniel S Marshall
Camilla M Hoyos
Zoe Menczel Schrire
Shantel L Duffy
Loren Mowszowski
Haley M La Monica
Julia L Chapman
Simon J G Lewis
author_facet Craig L Phillips
Sharon L Naismith
Ronald R Grunstein
Bandana Saini
Christopher J Gordon
Nathaniel S Marshall
Camilla M Hoyos
Zoe Menczel Schrire
Shantel L Duffy
Loren Mowszowski
Haley M La Monica
Julia L Chapman
Simon J G Lewis
author_sort Craig L Phillips
collection DOAJ
description Introduction Melatonin has multiple proposed therapeutic benefits including antioxidant properties, synchronisation of the circadian system and lowering of blood pressure. In this protocol, we outline a randomised controlled trial to assess the feasibility, acceptability and tolerability of higher dose (25 mg) melatonin to target brain oxidative stress and sleep disturbance in older adults with mild cognitive impairment (MCI).Methods and analysis The study design is a randomised double-blind, placebo-controlled, parallel group trial. Forty individuals with MCI will be recruited from the Healthy Brain Ageing Clinic, University of Sydney and from the community, and randomised to receive either 25 mg oral melatonin or placebo nightly for 12 weeks. The primary outcomes are feasibility of recruitment, acceptability of intervention and adherence to trial medication at 12 weeks. Secondary outcomes will include the effect of melatonin on brain oxidative stress as measured by magnetic resonance spectroscopy, blood pressure, blood biomarkers, mood, cognition and sleep. Outcomes will be collected at 6 and 12 weeks. The results of this feasibility trial will inform a future conclusive randomised controlled trial to specifically test the efficacy of melatonin on modifiable risk factors of dementia, as well as cognition and brain function. This will be the first trial to investigate the effect of melatonin in the population with MCI in this way, with the future aim of using this approach to reduce progression to dementia.Ethics and dissemination This protocol has been approved by the Sydney Local Health District Ethics Committee (X18-0077). This randomised controlled trial will be conducted in compliance with the protocol published in the registry, the International Conference for Harmonisation on Good Clinical Practice and all other applicable regulatory requirements. The findings of the trial will be disseminated via conferences, publications and media, as applicable. Participants will be informed of results of the study at the conclusion of the trial. Eligible authors will include investigators who are involved in the conception and design of the study, the conduct of the trial, the analysis of the results, and reporting and presentation of study findings.Trial registration number Australian and New Zealand Clinical Trials Registry (ANZCTRN 12619000876190).Protocol version V.8 15 October 2020.
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spelling doaj-art-dca53031a67a4cdca2686670b585ffc72024-11-17T14:25:08ZengBMJ Publishing GroupBMJ Open2044-60552021-02-0111210.1136/bmjopen-2020-041500Feasibility of 3-month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment: protocol for a randomised, placebo-controlled studyCraig L Phillips0Sharon L Naismith1Ronald R Grunstein2Bandana Saini3Christopher J Gordon4Nathaniel S Marshall5Camilla M Hoyos6Zoe Menczel Schrire7Shantel L Duffy8Loren Mowszowski9Haley M La Monica10Julia L Chapman11Simon J G Lewis122 Department of Respiratory and Sleep Medicine, Royal North Shore Hospital, St Leonards, New South Wales, AustraliaBrain and Mind Centre, The University of Sydney, Camperdown, New South Wales, AustraliaCPC-RPA clinic, Royal Prince Alfred Hospital, Sydney, New South Wales, AustraliaCentre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Macquarie University, Sydney, New South Wales, AustraliaCentre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Macquarie University, Sydney, New South Wales, AustraliaFaculty of Medicine and Health, University of Sydney, Sydney, New South Wales, AustraliaCIRUS, Centre for Sleep and Chronobiology, The Woolcock Institute of Medical Research, Camperdown, New South Wales, AustraliaHealthy Brain Ageing Program, The University of Sydney School of Psychology, Sydney, New South Wales, AustraliaCharles Perkins Centre, The University of Sydney, Sydney, New South Wales, AustraliaHealthy Brain Ageing Program, The University of Sydney School of Psychology, Sydney, New South Wales, AustraliaHealthy Brain Ageing Program, The University of Sydney School of Psychology, Sydney, New South Wales, AustraliaHealthy Brain Ageing Program, The University of Sydney School of Psychology, Sydney, New South Wales, AustraliaForeFront Parkinson’s Disease Research Clinic, Brain and Mind Centre, University of Sydney, Sydney, New South Wales, AustraliaIntroduction Melatonin has multiple proposed therapeutic benefits including antioxidant properties, synchronisation of the circadian system and lowering of blood pressure. In this protocol, we outline a randomised controlled trial to assess the feasibility, acceptability and tolerability of higher dose (25 mg) melatonin to target brain oxidative stress and sleep disturbance in older adults with mild cognitive impairment (MCI).Methods and analysis The study design is a randomised double-blind, placebo-controlled, parallel group trial. Forty individuals with MCI will be recruited from the Healthy Brain Ageing Clinic, University of Sydney and from the community, and randomised to receive either 25 mg oral melatonin or placebo nightly for 12 weeks. The primary outcomes are feasibility of recruitment, acceptability of intervention and adherence to trial medication at 12 weeks. Secondary outcomes will include the effect of melatonin on brain oxidative stress as measured by magnetic resonance spectroscopy, blood pressure, blood biomarkers, mood, cognition and sleep. Outcomes will be collected at 6 and 12 weeks. The results of this feasibility trial will inform a future conclusive randomised controlled trial to specifically test the efficacy of melatonin on modifiable risk factors of dementia, as well as cognition and brain function. This will be the first trial to investigate the effect of melatonin in the population with MCI in this way, with the future aim of using this approach to reduce progression to dementia.Ethics and dissemination This protocol has been approved by the Sydney Local Health District Ethics Committee (X18-0077). This randomised controlled trial will be conducted in compliance with the protocol published in the registry, the International Conference for Harmonisation on Good Clinical Practice and all other applicable regulatory requirements. The findings of the trial will be disseminated via conferences, publications and media, as applicable. Participants will be informed of results of the study at the conclusion of the trial. Eligible authors will include investigators who are involved in the conception and design of the study, the conduct of the trial, the analysis of the results, and reporting and presentation of study findings.Trial registration number Australian and New Zealand Clinical Trials Registry (ANZCTRN 12619000876190).Protocol version V.8 15 October 2020.https://bmjopen.bmj.com/content/11/2/e041500.full
spellingShingle Craig L Phillips
Sharon L Naismith
Ronald R Grunstein
Bandana Saini
Christopher J Gordon
Nathaniel S Marshall
Camilla M Hoyos
Zoe Menczel Schrire
Shantel L Duffy
Loren Mowszowski
Haley M La Monica
Julia L Chapman
Simon J G Lewis
Feasibility of 3-month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment: protocol for a randomised, placebo-controlled study
BMJ Open
title Feasibility of 3-month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment: protocol for a randomised, placebo-controlled study
title_full Feasibility of 3-month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment: protocol for a randomised, placebo-controlled study
title_fullStr Feasibility of 3-month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment: protocol for a randomised, placebo-controlled study
title_full_unstemmed Feasibility of 3-month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment: protocol for a randomised, placebo-controlled study
title_short Feasibility of 3-month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment: protocol for a randomised, placebo-controlled study
title_sort feasibility of 3 month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment protocol for a randomised placebo controlled study
url https://bmjopen.bmj.com/content/11/2/e041500.full
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