Contact information
Type
Scientific
Primary contact
Prof John Kirwan
ORCID ID
Contact details
Academic Rheumatology Unit
Bristol Royal Infirmary
Bristol
BS2 8HW
United Kingdom
+44 (0)117 928 2904
John.Kirwan@Bristol.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
ME/2005/2073
Study information
Scientific title
Acronym
Study hypothesis
Rheumatoid Arthritis (RA) is a systemic, inflammatory condition causing joint pain and swelling, disability, and psychological distress.
To document overnight variations of serum pro-inflammatory and anti-inflammatory cytokines in 12 volunteers with rheumatoid arthritis on one night before and one night during treatment with a Timed Release Tablet (TRT) containing 5 mg prednisone, and to relate blood cytokine levels to biogenic amines and the hormones of the hypothalamic-pituitary-adrenal axis.
Ethics approval
Approval received from the North Somerset and South Bristol Research Ethics Committee (REC) on the 28th November 2005 (ref: 054/Q2006/185).
Study design
Non-randomised, non-controlled interventional single centre study of patients before and after two weeks treatment with night time prednisone
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Rheumatoid Arthritis (RA)
Intervention
The study uses a delayed (timed) release formulation of prednisone which will release the full dose of the active drug during sleep after a lag time of 4 hours, allowing the patient to take the medication at a convenient point in time, namely at 22:00 hours +/- 30 minutes.
Intervention: Timed-Release Tablet (TRT) prednisone 5 mg, one tablet taken at 22.00 each evening for 12 - 16 nights (depending on the convenience of the final study night for the patient). There is no study follow-up after the end of medication.
Intervention type
Drug
Phase
Not Specified
Drug names
Prednisone
Primary outcome measure
Changes in overnight pattern of plasma cortisol and interleukin-6 concentrations, determined at baseline and two weeks.
Secondary outcome measures
Standard assessment tools will be used to assess the state of the patient's arthritis. These assessments will be:
1. Swollen and tender joint counts
2. Pain (visual analogue scale)
3. Morning stiffness (minutes)
4. Patient's opinion of condition
5. Clinician's opinion of condition
6. Health Assessment Questionnaire
7. The Multidimensional Assessment of Fatigue scale
8. Hospital Anxiety and Depression Scale
The secondary outcome measures are determined at baseline and two weeks.
Overall trial start date
15/06/2006
Overall trial end date
14/06/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Have rheumatoid arthritis by the criteria of the American College of Rheumatology
2. Are over 50 but less than 80 years old
3. Have active disease as evidenced by:
3.1. Three or more swollen joints
3.2. Three or more tender joints
3.3. Morning stiffness at least 45 minutes
3.4. Pain at least 30 mm on a 100 mm Visual Analogue Scale (VAS)
3.5. Erythrocyte Sedimentation Rate (ESR) at least 29 mm in first hour or C-Reactive Protein (CRP) at least 15 mg/L
4. Stable Disease-Modifying Anti-Rheumatic Drug (DMARD) therapy (or no therapy) for at least 28 days
5. Stable Non-Steroidal Anti-Inflammatory Drug (NSAID)/analgesic therapy for at least seven days
It is anticipated that the ratio of female to male patients will be approximately 2:1, in accordance with the pattern of disease occurrence. To be safe, we will invite women of childbearing potential to take part in the study only if they are using contraception.
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
12
Participant exclusion criteria
1. Pregnancy and lactation
2. Participation in a clinical trial within the past 30 days
3. Presence of contraindication of corticosteroids
4. Known hypersensitivity to prednisone/prednisolone
5. Parenteral treatment with corticosteroids or crystalloid injection into joints within the past three months
6. Other diseases which require corticoid treatments
7. Inflammatory diseases, such as Irritable Bowel Disease (IBD), Colitis, Crohn's Disease, Asthma
8. Other auto-immune diseases
9. Cancer
10. Infections, treatment with antibiotics within the past six weeks
11. Requirement of non-permitted concomitant medication
12. Consumption of benzodiazepines, antidepressants, antipsychotic drugs, antihistaminic drugs
13. Tumour Necrotising Factor - alpha (TNFα) inhibitors
14. Working shift employee
15. Jet lag
16. Significant renal disease (creatinine greater than 150 µmol/L)
17. Significant hepatic impairment
Recruitment start date
15/06/2006
Recruitment end date
14/06/2008
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Academic Rheumatology Unit
Bristol
BS2 8HW
United Kingdom
Sponsor information
Organisation
United Bristol Healthcare NHS Trust (UK)
Sponsor details
Marlborough Street
Bristol
BS2 8HW
United Kingdom
+44 (0)117 928 3473
Maria.Palmer@ubht.swest.nhs.uk
Sponsor type
Government
Website
Funders
Funder type
Industry
Funder name
Nitec Pharma AG (Switzerland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
1. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20398018
Publication citations
-
Results
Kirwan JR, Clarke L, Hunt LP, Perry MG, Straub RH, Jessop DS, Effect of novel therapeutic glucocorticoids on circadian rhythms of hormones and cytokines in rheumatoid arthritis., Ann. N. Y. Acad. Sci., 2010, 1193, 127-133, doi: 10.1111/j.1749-6632.2009.05289.x.