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ISRCTN
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ISRCTN59927814
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ClinicalTrials.gov identifier
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Public title
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Vitamin D and vascular health of Chronic Fatigue Syndrome patients
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Scientific title
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Vitamin D supplementation in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) patients: a randomised, placebo controlled, parallel, double blind study
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Acronym
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N/A
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Serial number at source
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2009CV08
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Study hypothesis
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Serum concentration of 25-hydroxyvitamin D (25[OH]D) levels are associated with important cardiovascular risk factors. Low levels of 25(OH)D are associated with hypertension, increased vascular resistance, increased left ventricular mass index, and increased coronary calcification.
Correlation between levels of inflammation and arterial stiffness has been reported in a population of 41 well-characterised patients with ME/CFS compared to 30 healthy subjects but vitamin D levels were not measured as part of that study done by University of Dundee.
We will investigate the relationship between vitamin D and arterial stiffness and inflammation and further examine various parts of the vitamin D pathway.
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Lay summary
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Ethics approval
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Applying to Tayside Research Ethics Committee
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Study design
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Randomised double blind placebo controlled parallel group study
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Countries of recruitment
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United Kingdom
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Disease/condition/study domain
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Myalgic Encephalomyelitis (ME); Chronic Fatigue Syndrome (CFS)
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Participants - inclusion criteria
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1. Patients diagnosed with ME/CFS (fulfils the Fukuda [1994] and Canadian [2003] criteria)
2. Serum 25(OH)D levels < 75 nmol/l
3. Male or female, aged 18 - 65
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Participants - exclusion criteria
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1. Patients not diagnosed with ME/CFS
2. Patients already taking Vitamin D supplements (fish oils will be permitted)
3. Estimated Glomerular Filtration Rate (GFR) < 40 mls/min (by MDRD4 method)
4. Adjusted serum calcium < 2.15 or > 2.60 mmol/L
5. Liver Function Test (LFT) > 3x upper limit of normal (ULN)
6. Known metastatic malignancy
7. History of Kidney stones
8. History of sarcoidosis or osteoporosis
9. Lying systolic blood pressure (BP) < 80 mm Hg
10. Pregnant, lactating or of childbearing age and not taking reliable contraception
11. Patients diagnosed with psychiatric disorder (including depression) within the past five years
12. Patients diagnosed with schizophrenia, mania, substance abuse/dependence, or an eating disorder at any time
13. Patients with other known organic cause for their symptoms
14. Unable to give written informed consent
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Anticipated start date
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01/04/2010
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Anticipated end date
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01/04/2011
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Status of trial
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Completed |
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Patient information material
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Not available in web format, please use contact details below to request a patient information sheet.
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Target number of participants
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50
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Interventions
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In total there will be 5 visits in this study. Screening, baseline visit, and visit during month 2, 4 and 6. Screening visit will involve taking written informed consent, physical examination, medical history to diagnose CFS and to check inclusion / exclusion criteria. Baseline visit will involve dosing of 100,000 unit of cholecalciferol or matching placebo and taking blood for baseline biomarkers, PAT (Peripheral Arterial Tonometry), blood pressure (BP) and electrocardiography (ECG). The dose of cholecalciferol will be repeated during 2nd and 4th month visits. Activities during 2nd month and 6th month visit will be identical to baseline visit. 4th month visit will involve only dosing and review of adverse events (AE).
The total duration of this study is 18 months.
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Primary outcome measure(s)
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Arterial stiffness, assessed at baseline, 2 and 6 months:
Blood pressure will be measured in triplicate using an automated blood pressure monitor (Omron705 CPII). Peripheral pressure waveforms will be recorded at the radial, femoral and carotid artery using the validated SphygmoCor pulse waveform analysis system (AtCor Medical). We will calculate the carotid to femoral and carotid to radial pulse wave velocity, and additionally the augmentation index.
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Secondary outcome measure(s)
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1. Endothelial function, assessed at baseline, 2 and 6 months
Flow mediated dilation of the brachial artery will be measured according to standard guidelines.37 The diameter of the brachial artery will be measured using a 7.5-15 MHz linear array transducer. Baseline images are taken for 1 minute. A blood pressure cuff is then placed around the arm and inflated to a suprasystolic pressure for 5 minutes. ECG-triggered images are after captured for 3 minutes after cuff release. Once a stable baseline has been re-established, sublingual nitroglycerine (NTG) (0.4 mg) is administered and endothelium-independent vasodilation is assessed in a similar fashion.
2. Vascular biomarkers, assessed at baseline, 2 and 6 months
2.1. Fasting serum lipid profiles, measured using COBAS Bio Autoanalyser
2.2. Fasting glucose and insulin levels. Estimates of insulin resistance will be calculated using the Homeostasis Model (HOMA) (fasting glucose x fasting insulin/22.5).
2.3. High sensitivity C-reactive protein (CRP), measured by Enzyme Linked Immunosorbent Assay (ELISA)
2.4. Tumour necrosis factor-alpha (TNF-α), measured by ELISA
2.5. Interleukin-6 (IL-6), measured by ELISA
2.6. Serum 25-hydroxyvitamin-D3 (25[OH]D), measured by ELISA
2.7. 1,25-dihydroxy vitamin D3 (1,25-[OH]2D3), measured by ELISA
3. Fatigue, measured using the Piper Fatigue Scale
4. Quality of life, assessed using the Medical Outcomes Study (MOS) SF-36
5. Emotional adjustment, assessed using the Hospital Anxiety and Depression Scale (HADS)
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Sources of funding
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ME Research UK (UK)
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Trial website
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Publications
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Contact name
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Prof
JJF
Belch
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Address
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Professor of Vascular Medicine
The Institute of Cardiovascular Research
Ninewells Hospital
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City/town
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Dundee
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Zip/Postcode
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DD1 9SY
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Country
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United Kingdom
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Sponsor
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University of Dundee (UK)
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Address
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c/o Dr James Houston
Research and Innovation Services
Ninewells Hospital
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City/town
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Dundee
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Zip/Postcode
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DD1 9SY
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Country
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United Kingdom
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Date applied
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10/02/2010
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Last edited
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18/03/2010
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Date ISRCTN assigned
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18/03/2010
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