Rescue of Addison’s disease 2
- Conditions
- Autoimmune Addison's disease: autoimmune primary adrenal insufficiencyMedDRA version: 16.1 Level: PT Classification code 10052381 Term: Primary adrenal insufficiency System Organ Class: 10014698 - Endocrine disordersMedDRA version: 16.1 Level: LLT Classification code 10001335 Term: Adrenal cortex insufficiency System Organ Class: 10014698 - Endocrine disordersMedDRA version: 16.1 Level: LLT Classification code 10001342 Term: Adrenal cortical hypofunction System Organ Class: 10014698 - Endocrine disordersTherapeutic area: Diseases [C] - Hormonal diseases [C19]
- Registration Number
- EUCTR2012-001682-33-GB
- Lead Sponsor
- ewcastle upon Tyne Hospitals NHS Foundation Trust
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 17
- Clear evidence of adrenocortical failure with subnormal cortisol response to 250?g IV synacthen (peak cortisol <300nmol/l) plus either clinical or biochemical evidence to confirm elevated ACTH, or evidence of mineralcorticoid insufficiency
- Basal or ACTH stimulated serum cortisol >50nmol/l
- Patients are less than 8 weeks from first diagnosis of AAD
- Positive serum 21-hydroxylase autoantibodies (>1.0 IU/l on RSR assay)
- Normal or atrophic adrenal glands on CT scan
- Willingness to travel to the relevant site for study
- Willingness to attend education sessions about indications for parenteral glucocorticoid administration and technique of administration.
Are the trial subjects under 18? yes
Number of subjects for this age range: 4
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 26
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
- Active viral illness, including HIV, Hepatitis B or C, shingles/Zoster
- Recent or partially treated TB or unexplained radiographic abnormality on chest X-ray
- Previous use of immunosuppressive or cytotoxic drugs (excluding glucocorticoid)
- Significant cardio-respiratory (inc. asthma), chronic renal or non-autoimmune liver disease
- Pregnant or breastfeeding and with no plan for pregnancy/ breastfeeding within 24 months
- Allergy to synacthen, synacthen depot, rituximab or methylprednisolone
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Main Objective: The primary objective is to restore adrenal function in patients with recent onset autoimmune Addison's disease. This study will answer the following questions:<br><br> In people with new-onset autoimmune Addison’s disease will the therapeutic regimen of rituximab and ACTH allow improvement or recovery of adrenal function?<br><br> ;<br> Secondary Objective: •Will this therapeutic regimen result in amelioration of the humoral immune response by reducing autoantibody titres?<br> •What are the adverse effects of this therapeutic regimen?<br> •Will the regimen be acceptable and well-tolerated by patients?<br> •What is the early natural history of conventionally treated AAD?<br> ;Primary end point(s): Peak serum cortisol in response to IM synacthen testing at 48 weeks.;Timepoint(s) of evaluation of this end point: 48 weeks post first treatment
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): - Restoration of normal glucocorticoid secretion (peak cortisol >550nmol/l after repeat synacthen testing at 6, 12, 24, and 72 weeks)<br> - Improvement of basal and peak cortisol response (>100nmol/l over baseline) to synacthen testing<br> - Normalisation of ACTH, DHEAS, 17a OH-progesterone and recumbent renin and aldosterone levels<br> ;Timepoint(s) of evaluation of this end point: at 6,12,24, 48 and 72 weeks