Circadian variations in cytokines and the effect of timed release tablet prednisone in rheumatoid arthritis

ISRCTN	ISRCTN17552423
DOI	https://doi.org/10.1186/ISRCTN17552423
Secondary identifying numbers	ME/2005/2073

Submission date: 16/08/2007
Registration date: 04/10/2007
Last edited: 18/01/2012

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof John Kirwan
Scientific

Academic Rheumatology Unit
Bristol Royal Infirmary
Bristol
BS2 8HW
United Kingdom

Phone	+44 (0)117 928 2904
Email	John.Kirwan@Bristol.ac.uk

Study information

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
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title
Study objectives	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(s)	Approval received from the North Somerset and South Bristol Research Ethics Committee (REC) on the 28th November 2005 (ref: 054/Q2006/185).
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	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 study start date	15/06/2006
Completion date	14/06/2008

Eligibility

Participant type(s)	Patient
Age group	Senior
Sex	Both
Target number of participants	12
Key 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.
Key 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
Date of first enrolment	15/06/2006
Date of final enrolment	14/06/2008

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Academic Rheumatology Unit

Bristol
BS2 8HW
United Kingdom

Sponsor information

United Bristol Healthcare NHS Trust (UK)
Hospital/treatment centre

Marlborough Street
Bristol
BS2 8HW
England
United Kingdom

Phone	+44 (0)117 928 3473
Email	Maria.Palmer@ubht.swest.nhs.uk
Website	http://www.ubht.nhs.uk/R&D/
"ROR"	https://ror.org/04nm1cv11

Funders

Funder type

Industry

Nitec Pharma AG (Switzerland)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/04/2010		Yes	No