Rescue of ADdiSons disease 2
| ISRCTN | ISRCTN20220821 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN20220821 |
| Secondary identifying numbers | RADS2v2.1:08/12 |
- Submission date
- 26/09/2012
- Registration date
- 23/10/2012
- Last edited
- 05/01/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims:
Addisons disease is caused by an autoimmune attack leading to destruction of the adrenal glands. RADS2 aims to prevent the autoimmune attack on the adrenal gland and stimulate re-growth and regeneration of adrenal function.
Who can participate?
Patients aged 10 to 65 years, diagnosed with autoimmune Addisons disease within the previous 28 days.
What does the study involve?
Two infusions of rituximab are given, each lasting 6 hours. Also, alternate day injections of an adrenal gland stimulating hormone, ACTH are given.
What are the possible benefits and risks of participating?
The benefit is that your adrenal failure might go into remission, or even be cured. The risk is that the trial medication wont work, or that you could have a reaction to it.
Where is the study run from?
Newcastle University, UK, with participating centres in Cambridge and Exeter, UK.
When is study starting and how long is it expected to run for?
November 2012, running for 4 years.
Who is funding the study?
Medical Research Council, UK.
Who is the main contact?
Prof Simon Pearce
s.h.s.pearce@ncl.ac.uk
Contact information
Scientific
Institute of Genetic Medicine
Newcastle University
International Centre for Life
Newcastle upon Tyne
NE1 3BZ
United Kingdom
| Phone | +44 (0)191 2418674 |
|---|---|
| s.h.s.pearce@ncl.ac.uk |
Study information
| Study design | Multicentre study conducted in 2 parts Part A: Open-label interventional study of rituximab and synacthen Part B: Observational study of the natural history of autoimmune Addisons disease |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised controlled trial |
| Study setting(s) | Hospital |
| 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 | Combined immunotherapy and trophic adrenocortical stimulation in new onset autoimmune Addisons disease |
| Study acronym | RADS2 |
| Study objectives | This study will answer the following principal questions: In people with new-onset autoimmune Addisons disease, who have residual steroidogenic capacity: 1. Will the therapeutic regimen of rituximab and adrenocorticotropic hormone (ACTH) allow improvement or recovery of adrenocortical function? 2. Will this therapeutic regimen result in amelioration of the humoral immune response by reducing autoantibody titres? 3. What are the adverse effects of this therapeutic regimen? 4. Will the regimen be acceptable and well-tolerated by patients? 5. What is the early natural history of conventionally treated autoimmune Addisons disease (AAD)? |
| Ethics approval(s) | National Research Ethics Service (NRES) Committee North East - Sunderland, 24 September 2012, ref: 12/NE/0339 |
| Health condition(s) or problem(s) studied | Autoimmune Addison's disease |
| Intervention | Part A 1. Subjects will receive 125mg IV methylprednisolone followed by 1g IV rituximab on day 1 & day 15. 2. Depot synacthen 1mg will be self-administered on alternate days (week 1-12, followed by an 8 week tail) 3. Daily oral hydrocortisone and fludrocortisone will continue in regular replacement doses (eg. Hydrocortisone 10 & 5mg, or 10 & 5 & 5mg; fludrocortisone 50-150 ìg) 4. Adrenal function, circulating B cell numbers, adrenal autoantibody titres and wellbeing will be assessed at baseline, 6, 12, 24, 48, and 72 weeks. 5. Replacement steroids will be weaned off, if serum cortisol concentrations improve to >400nmol/l. The last (72 week) visit of the last participant will mark the end of the study Part B: Observation only 1. Adrenal function, adrenal autoantibodies and wellbeing will be assessed at baseline & 48 weeks. 2. The last (48 week) visit of the last participant will mark the end of the study for these participants. |
| Intervention type | Other |
| Primary outcome measure | Restoration of normal glucocorticoid secretion (peak cortisol >550nmol/l after repeat synacthen testing at 48 weeks) |
| Secondary outcome measures | 1. Restoration of normal glucocorticoid secretion (peak cortisol >550nmol/l after repeat synacthen testing at 6,12, 24, and 72 weeks) 2. Improvement of basal and peak cortisol response (>100nmol/l over baseline) to synacthen testing 3. Normalisation of ACTH, Dehydroepiandrosterone (DHEAS), 17á OH-progesterone and recumbent renin and aldosterone levels |
| Overall study start date | 01/11/2012 |
| Completion date | 31/10/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Part A (15 participants); part B ( 15 participants) |
| Total final enrolment | 13 |
| Key inclusion criteria | Part A: 1. Clear evidence of adrenocortical failure with subnormal cortisol response to 250 µg IV synacthen (peak cortisol <300nmol/l) plus either clinical or biochemical evidence to confirm elevated ACTH, or evidence of mineralcorticoid insufficiency 2. Basal or ACTH stimulated serum cortisol >50nmol/l 3. Patients are less than 4 weeks from first diagnosis of AAD 4. Positive serum 21-hydroxylase autoantibodies (>1.0 IU/l on RSR assay) 5. Normal or atrophic adrenal glands on CT scan 6. Willingness to travel to the Wilson Horne Immunotherapy Centre, Newcastle for study 7. Willingness to attend education sessions about indications for parenteral glucocorticoid administration and technique of administration 8. Willingness to use secure contraception during and for 12 months post-treatment with rituximab ((women of childbearing potential) For Part B, only the first 4 criteria are relevant |
| Key exclusion criteria | 1. Active viral illness, including HIV, Hepatitis B or C, shingles/Zoster 2. Recent or partially treated TB or unexplained radiographic abnormality on chest X-ray 3 .Previous use of immunosuppressive or cytotoxic drugs (excluding glucocorticoid) 4. Significant cardio-respiratory (inc. asthma), chronic renal or non-autoimmune liver disease 5. Pregnant or breastfeeding and with plan for pregnancy/ breastfeeding within 24 months 6. Known allergy or contraindication to synacthen, synacthen depot, rituximab or methylprednisolone |
| Date of first enrolment | 01/11/2012 |
| Date of final enrolment | 31/10/2016 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
NE1 3BZ
United Kingdom
Sponsor information
Hospital/treatment centre
Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
England
United Kingdom
| amanda.tortice@ncl.ac.uk | |
| Website | http://www.newcastle-hospitals.org.uk/ |
"ROR" |
https://ror.org/05p40t847 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
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 | 01/04/2020 | 30/10/2020 | Yes | No |
| Results article | results | 01/04/2020 | 05/01/2021 | Yes | No |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
05/01/2021: Publication reference added.
30/10/2020: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
