PB-DEPIST: Screening for Adrenal Insufficiency During Dermocorticoid Reduction in Bullous Pemphigoid (BP)

Sponsor

University Hospital, Bordeaux (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06148090

Collaborator

(none)

Enrollment

Location

Arm

25.3

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Pemphigoid, Bullous Adrenal Insufficiency	Diagnostic Test: clobetasol decreasing measurement	N/A

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

At two occasions during the clobetasol decreasing, cortisol and ionogram 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 A third visit (visit 3) is necessary if blood cortisol is between 138 and 500 nmol/L, to make a Synacthen® test (new cortisol dosage at 8 AM, then IM or IV injection of a 250 microgram ampoule of Synacthen® completed by a 2nd cortisol dosage one hour later)At two occasions during the clobetasol decreasing, cortisol and ionogram 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 A third visit (visit 3) is necessary if blood cortisol is between 138 and 500 nmol/L, to make a Synacthen® test (new cortisol dosage at 8 AM, then IM or IV injection of a 250 microgram ampoule of Synacthen® completed by a 2nd cortisol dosage one hour later)

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Screening for Adrenal Insufficiency During Dermocorticoid Reduction in Bullous Pemphigoid

Anticipated Study Start Date :

Nov 22, 2023

Anticipated Primary Completion Date :

Dec 30, 2025

Anticipated Study Completion Date :

Dec 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treated with clobetasol propionate	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

Arm

Intervention/Treatment

Experimental: Treated with clobetasol propionate

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

Outcome Measures

Primary Outcome Measures

Measure of cortisol concentration in serum [Month 1]
Cortisol concentration in serum, after at least 1 month treatment with 20-40g of clobetasol twice a week
Measure of cortisol concentration in serum [Month 2]
Cortisol concentration in serum, after at least 1 month treatment with 20-40g of clobetasol one a week
Measure of cortisol concentration in serum after Adreno CorticoTropic Hormone (ACTH) stimulation test (Synacthen®) [Month 1]
ACTH stimulation test is necessary if serum cortisol concentration is found between 138 and 500 nmol/L
Measure of cortisol concentration in serum after ACTH stimulation test (Synacthen®) [Month 2]
ACTH stimulation test is necessary if serum cortisol concentration is found between 138 and 500 nmol/L

Secondary Outcome Measures

Measure of glucose concentration in blood [Month 1]
Searching for a biological sign of adrenal insufficiency : hypoglycemia
Measure of glucose concentration in blood [Month 2]
Searching for a biological sign of adrenal insufficiency : hypoglycemia
Measure of sodium concentration in blood [Month 1]
Searching for a biological sign of adrenal insufficiency : hyponatremia
Measure of sodium concentration in blood [Month 2]
Searching for a biological sign of adrenal insufficiency : hyponatremia
Measure of blood pressure [Month 1]
Searching for a clinical sign of adrenal insufficiency : low blood pressure
Measure of blood pressure [Month 2]
Searching for a clinical sign of adrenal insufficiency : low blood pressure
Evaluation of skin atrophy (actinic purpura, skin thinness, post-blister erosion) [Month 1]
Evaluation of skin, looking for factors increasing clobetasol absorption and/or predicting adrenal insufficiency
Evaluation of skin atrophy (actinic purpura, skin thinness, post-blister erosion) [Month 2]
Evaluation of skin, looking for factors increasing clobetasol absorption and/or predicting adrenal insufficiency
Measure of Weight [Month 1]
Evaluating if low body mass index increases clobetasol absorption and/or predicts adrenal insufficiency
Measure of Weight [Month 2]
Evaluating if low body mass index increases clobetasol absorption and/or predicts adrenal insufficiency
Measure of Height [Month 1]
Evaluating if low body mass index increases clobetasol absorption and/or predicts adrenal insufficiency
Measure of Height [Month 2]
Evaluating if low body mass index increases clobetasol absorption and/or predicts adrenal insufficiency
Measure of Quantity of clobetasol applied per week [Month 1]
Evaluating if the risk of adrenal insufficiency depends of the quantity and/or duration of clobetasol treatment
Measure of Quantity of clobetasol applied per week [Month 2]
Evaluating if the risk of adrenal insufficiency depends of the quantity and/or duration of clobetasol treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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