Screening for Adrenal Insufficiency During Dermocorticoid Reduction in Bullous Pemphigoid (BP)

Adrenal Insufficiency Clinical Trial

— PB-DEPIST  

Official title:

Screening for Adrenal Insufficiency During Dermocorticoid Reduction in Bullous Pemphigoid

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06148090
• Other study ID #: CHUBX 2023/07
• Status: Recruiting
• Phase: N/A
• Start date: January 4, 2024
• Est. completion date: January 1, 2026

Study information

• Verified date: February 2024
• Source: University Hospital, Bordeaux
• Contact: Anne Pham-Ledard, MD, PhD
• Phone: +335 56 79 56 79
• Email: anne.pham-ledard[@]chu-bordeaux.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The braking of the corticotropic axis is well established during the induction phase of superpotent topical corticosteroid therapy (clobetasol propionate) in bullous pemphigoid (BP). But the evolution of the corticotropic axis in the following months, especially during the tapering of topical steroids has never been studied. The objective of this study is to evaluate the prevalence of adrenal insufficiency during the topical corticosteroid therapy tapering in patients treated according to current recommendations.

The secondary objectives of the study are :

• to evaluate the presence of other clinico-biological signs of adrenal insufficiency (hypotension, hypoglycemia and/or hyponatremia)

• to compare the characteristics of patients with adrenal insufficiency to those without in order to identify potential risk factors for adrenal insufficiency in BP.

Description:

BP is the most common autoimmune bullous dermatosis, with 400 incident cases per year in France and an estimated annual mortality rate of 30%. It affects very old and frail patients, with an average age of 80 years.

High potency topical corticosteroids is the first line therapy, with a high dose applied to the entire tegument for at least 4 months according to current guidelines. In this high potency topical therapy, a braking of the corticotropic axis has been reported during the initial phase of treatment, at the highest doses, explained by the transdermal and systemic passage of dermocorticoids. Monitoring if natural cortisol secretion will start again has never been studied during the tapering of topical corticosteroid therapy, and its under-diagnosis could be deleterious for patients. The French guidelines currently recommends hydrocortisone supplementation at the time of waning from less than 20 g of clobetasol propionate per week, but without any data supporting it.

Prospective multicenter study coordinated by the Bordeaux Dermatology Department and conducted within the French study Group on autoimmune bullous diseases, will aim to include 50 patients with a diagnosis of bullous pemphigoid and treated according to recommendations.

Serum dosage of Cortisol concentration will be measured on two occasions, at the last two steps of the corticosteroid tapering (20-40g, twice a week and 20-40g once a week). If necessary, a Synacthen® test will be performed in addition.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 1, 2026
• Est. primary completion date: January 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

Inclusion Criteria:

• Male or female at least 18 years of age

• BP diagnosis with at least 3 of the following 4 criteria:

• Age greater than 70 years

• Absence of mucosal involvement

• Absence of atrophic scarring

• No predominance of head and neck

• Skin biopsy with subepidermal cleavage and :

• FD with Ig and/or C3 deposits along the basement membrane

• And/or positive serum anti-BP180 and/or anti-BP230 antibodies

• Treated with clobetasol propionate, with or without background treatment (methotrexate, mycophenolate mofetil, IV Ig, omalizumab, rituximab)

• Treatment with clobetasol propionate 0.05%, 20 to 40 g per application, twice a week for at least one month

• Affiliated to a social security regimen ( without AME)

• Free, informed and expressed consent (confirmed in writing)

Exclusion Criteria:

• Old or ongoing adrenal insufficiency

• Systemic corticosteroid therapy of more than 1 month in the previous 3 months and/or more than 3 months in the previous 12 months, or in the 7 days prior to the cortisol test

• Immuno-induced bullous pemphigoid (anti-PD1, PDL1 and/or anti-CTLA4)

• Impossible to perform a blood test between 7:30 and 8:30 am

Related Conditions & MeSH terms

• Adrenal Insufficiency
• Pemphigoid, Bullous

Intervention

Diagnostic Test:
• clobetasol decreasing measurement
At two occasions during the clobetasol decreasing measurement at 8 AM and clinical assessment by a physician: Visit 1: 20-40 g clobetasol twice a week for at least 1 month Visit 2: 20-40 g clobetasol once a week for at least 1 month

Locations

Country	Name	City	State
France	University Hospital of Bordeaux - Hospital Saint André	Bordeaux
France	CH de Libourne	Libourne
France	CHU de Limoges	Limoges
France	Hôpital Saint louis	Paris
France	CHU de Rouen	Rouen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure of cortisol concentration in serum	Cortisol concentration in serum, after at least 1 month treatment with 20-40g of clobetasol twice a week	Month 1
Primary	Measure of cortisol concentration in serum	Cortisol concentration in serum, after at least 1 month treatment with 20-40g of clobetasol one a week	Month 2
Primary	Measure of cortisol concentration in serum after Adreno CorticoTropic Hormone (ACTH) stimulation test (Synacthen®)	ACTH stimulation test is necessary if serum cortisol concentration is found between 138 and 500 nmol/L	Month 1
Primary	Measure of cortisol concentration in serum after ACTH stimulation test (Synacthen®)	ACTH stimulation test is necessary if serum cortisol concentration is found between 138 and 500 nmol/L	Month 2
Secondary	Measure of glucose concentration in blood	Searching for a biological sign of adrenal insufficiency : hypoglycemia	Month 1
Secondary	Measure of glucose concentration in blood	Searching for a biological sign of adrenal insufficiency : hypoglycemia	Month 2
Secondary	Measure of sodium concentration in blood	Searching for a biological sign of adrenal insufficiency : hyponatremia	Month 1
Secondary	Measure of sodium concentration in blood	Searching for a biological sign of adrenal insufficiency : hyponatremia	Month 2
Secondary	Measure of blood pressure	Searching for a clinical sign of adrenal insufficiency : low blood pressure	Month 1
Secondary	Measure of blood pressure	Searching for a clinical sign of adrenal insufficiency : low blood pressure	Month 2
Secondary	Evaluation of skin atrophy (actinic purpura, skin thinness, post-blister erosion)	Evaluation of skin, looking for factors increasing clobetasol absorption and/or predicting adrenal insufficiency	Month 1
Secondary	Evaluation of skin atrophy (actinic purpura, skin thinness, post-blister erosion)	Evaluation of skin, looking for factors increasing clobetasol absorption and/or predicting adrenal insufficiency	Month 2
Secondary	Measure of Weight	Evaluating if low body mass index increases clobetasol absorption and/or predicts adrenal insufficiency	Month 1
Secondary	Measure of Weight	Evaluating if low body mass index increases clobetasol absorption and/or predicts adrenal insufficiency	Month 2
Secondary	Measure of Height	Evaluating if low body mass index increases clobetasol absorption and/or predicts adrenal insufficiency	Month 1
Secondary	Measure of Height	Evaluating if low body mass index increases clobetasol absorption and/or predicts adrenal insufficiency	Month 2
Secondary	Measure of Quantity of clobetasol applied per week	Evaluating if the risk of adrenal insufficiency depends of the quantity and/or duration of clobetasol treatment	Month 1
Secondary	Measure of Quantity of clobetasol applied per week	Evaluating if the risk of adrenal insufficiency depends of the quantity and/or duration of clobetasol treatment	Month 2