Condition category
Nutritional, Metabolic, Endocrine
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status

Plain English Summary

Background and study aims:
Addison’s 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 Addison’s 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 won’t 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

Trial website

Contact information



Primary contact

Prof Simon Pearce


Contact details

Institute of Genetic Medicine
Newcastle University
International Centre for Life
Newcastle upon Tyne
United Kingdom
+44 (0)191 2418674

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Combined immunotherapy and trophic adrenocortical stimulation in new onset autoimmune Addison’s disease



Study hypothesis

This study will answer the following principal questions:
In people with new-onset autoimmune Addison’s 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 Addison’s disease (AAD)?

Ethics approval

National Research Ethics Service (NRES) Committee North East - Sunderland, 24 September 2012, ref: 12/NE/0339

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 Addison’s disease

Primary study design


Secondary study design

Non randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Autoimmune Addison's disease


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



Not Applicable

Drug names

Primary outcome measures

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 trial start date


Overall trial end date


Reason abandoned


Participant 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

Participant type


Age group




Target number of participants

Part A (15 participants); part B ( 15 participants)

Participant 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

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Institute of Genetic Medicine
Newcastle upon Tyne
United Kingdom

Sponsor information


Newcastle upon Tyne Hospitals Foundation NHS Trust (UK)

Sponsor details

Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
United Kingdom

Sponsor type

Hospital/treatment centre



Funder type

Research council

Funder name

Medical Research Council (MRC) (UK) ref: MR/J002526

Alternative name(s)


Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit


United Kingdom

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes