Vitamin D and vascular health of chronic fatigue syndrome patients
| ISRCTN | ISRCTN59927814 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN59927814 |
| EudraCT/CTIS number | 2010-019096-29 |
| Secondary identifying numbers | 2009CV08 |
- Submission date
- 10/02/2010
- Registration date
- 18/03/2010
- Last edited
- 01/11/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims
Vitamin D levels are commonly low in patients with chronic fatigue syndrome and these patients can also have poor vascular health. The aim of this study is to test whether high-dose intermittent oral vitamin D therapy given every two months for six months could improve markers of vascular health and fatigue in patients with chronic fatigue syndrome.
Who can participate?
Patients aged 18 - 65 with chronic fatigue syndrome
What does the study involve?
Participants are randomly allocated to receive 100,000 units oral vitamin D3 or a matching placebo (dummy) treatment every 2 months for 6 months. Blood vessel function is assessed using non-invasive methods at a visit before receiving vitamin D3 and at the final 6-month visit. Other tests undertaken by participants are flow-mediated dilatation of the brachial artery; blood pressure, cholesterol, insulin resistance, markers of inflammation and oxidative stress are tested at the start of the study and repeated at 6 months, and each participant completes a fatigue questionnaire before and after 6 months in the study.
What are the possible benefits and risks of participating?
Potential risks of taking part include a risk of low calcium blood levels with high dose vitamin D3 but participants are monitored regularly.
Where is the study run from?
Ninewells Hospital (UK)
When is the study starting and how long is it expected to run for?
April 2010 to April 2011
Who is funding the study?
ME Research UK
Who is the main contact?
Prof. JJF Belch
Contact information
Scientific
The Institute of Cardiovascular Research
Ninewells Hospital
Dundee
DD1 9SY
United Kingdom
Study information
| Study design | Randomised double-blind placebo-controlled parallel-group study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Vitamin D supplementation in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients: a randomised, placebo-controlled, parallel, double-blind study |
| Study hypothesis | 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. This study will investigate the relationship between vitamin D and arterial stiffness and inflammation and further examine various parts of the vitamin D pathway. |
| Ethics approval(s) | Fife & Forth Valley Research Ethics Committee 2 (now called East of Scotland Research Ethics Service REC 2), 15/02/2011, REC ref: 10/SO501/61 |
| Condition | Myalgic Encephalomyelitis (ME); Chronic Fatigue Syndrome (CFS) |
| Intervention | In total there will be five visits in this study: screening, baseline visit, and visits during months 2, 4 and 6. The screening visit will involve taking written informed consent, a physical examination, medical history to diagnose CFS and to check inclusion/exclusion criteria. The baseline visit will involve dosing of 100,000 unit of cholecalciferol or matching placebo and taking blood for baseline biomarkers, Peripheral Arterial Tonometry (PAT), blood pressure (BP) and electrocardiography (ECG). The dose of cholecalciferol will be repeated during the 2nd and 4th month visits. Activities during 2nd month and 6th month visit will be identical to the baseline visit. The 4th month visit will involve only dosing and review of adverse events (AE). The total duration of this study is 18 months. |
| Intervention type | Supplement |
| Primary outcome measure | 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). The carotid to femoral and carotid to radial pulse wave velocity will be calculated, and additionally the augmentation index. |
| Secondary outcome measures | 1. Endothelial function, assessed at baseline, 2 and 6 months: Flow-mediated dilation of the brachial artery will be measured according to standard guidelines. 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-dihydroxyvitamin 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) |
| Overall study start date | 01/04/2010 |
| Overall study end date | 01/09/2012 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 50 |
| Participant inclusion criteria | 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 |
| Participant exclusion criteria | 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 ml/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 5 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 |
| Recruitment start date | 01/08/2011 |
| Recruitment end date | 01/03/2012 |
Locations
Countries of recruitment
- Scotland
- United Kingdom
Study participating centre
DD1 9SY
United Kingdom
Sponsor information
University/education
c/o Catrina Forde PhD
Tayside Medical Science Centre
Ninewells Hospital & Medical School
Research & Development Office
Residency Block, Level 3
George Pirie Way
Dundee
DD1 9SY
Scotland
United Kingdom
"ROR" |
https://ror.org/03h2bxq36 |
|---|
Funders
Funder type
Charity
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Faisel Khan (f.khan@dundee.ac.uk). Access to data will be subject to entering into collaboration with the investigators for non-commercial, bona fide academic analyses; decisions on data access will be made between the investigators and the Sponsor (University of Dundee). Participant consent for unrestricted sharing of individual participant data was not obtained. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/03/2015 | Yes | No | |
| Basic results | 18/10/2017 | 01/11/2017 | No | No |
Additional files
- ISRCTN59927814_BasicResults_18Oct17.pdf
- Uploaded 01/11/2017
Editorial Notes
01/11/2017: The basic results of this trial have been uploaded as an additional file.
19/10/2017: The overall trial end date was changed from 01/04/2011 to 01/09/2012.
22/12/2015: Publication reference added.
