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

Screening for Adrenal Insufficiency During Dermocorticoid Reduction in Bullous Pemphigoid

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.

Study Overview

• Status: Recruiting
• Conditions: Pemphigoid, Bullous; Adrenal Insufficiency
• Intervention / Treatment: Diagnostic test: clobetasol decreasing measurement

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 Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne Pham-Ledard, MD, PhD; Phone Number: +335 56 79 56 79; Email: anne.pham-ledard@chu-bordeaux.fr
• Study Contact Backup: Name: Christine Alfaro; Phone Number: +335 56 79 56 79; Email: christine.alfaro@chu-bordeaux.fr

Study Locations

• France
  • Bordeaux, France, 33000
    • Recruiting
    • University Hospital of Bordeaux - Hospital Saint André
    • Contact: Anne PHAM-LEDARD, MD, PhD; Phone Number: +335 56 79 49 52; Email: anne.pham-ledard@chu-bordeaux.fr
    • Contact: Christine ALFARO; Phone Number: +335 56 79 49 52; Email: christine.alfaro@chu-bordeaux.fr
    • Principal Investigator: Anne PHAM-LEDARD, MD, PhD
    • Sub-Investigator: Marie BEYLOT-BARRY, MD, PhD
    • Sub-Investigator: Julien SENESCHAL, MD, PhD
  • Libourne, France, 33500
    • Recruiting
    • CH de Libourne
    • Contact: Marie-Laure BOUYSSOU-GAUTHIER, MD; Email: Marie-Laure.Bouyssou-Gauthier@ch-libourne.fr
    • Principal Investigator: Marie-Laure BOUYSSOU-GAUTHIER, MD
    • Sub-Investigator: Alyssa BENARFA, MD
  • Limoges, France, 87000
    • Recruiting
    • CHU de Limoges
    • Contact: Jean-Philippe BERNARD, MD; Email: philippe.bernard@chu-limoges.fr
    • Principal Investigator: Jean-Philippe BERNARD, MD
    • Sub-Investigator: Emilie MIO BERTOLO, MD
  • Paris, France
    • Recruiting
    • Hopital Saint Louis
    • Contact: Emmanuelle TANCREDE-BOHIN, MD; Email: emmanuelle.tancrede-bohin@aphp.fr
    • Principal Investigator: Emmanuelle TANCREDE-BOHIN, MD
    • Sub-Investigator: Clemence LEPELLETIER-BEAUFOND, MD
  • Rouen, France, 76000
    • Recruiting
    • CHU de Rouen
    • Principal Investigator: Pascal JOLY, MD, PhD
    • Contact: Pascal JOLY, MD, PhD; Email: pascal.joly@chu-rouen.fr
    • Sub-Investigator: Julie BOUTEILLER, MD
    • Sub-Investigator: Vivien HEBBERT, MD
    • Sub-Investigator: Billal TEDBIRT, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of glucose concentration in blood	Searching for a biological sign of adrenal insufficiency : hypoglycemia	Month 1
Measure of glucose concentration in blood	Searching for a biological sign of adrenal insufficiency : hypoglycemia	Month 2
Measure of sodium concentration in blood	Searching for a biological sign of adrenal insufficiency : hyponatremia	Month 1
Measure of sodium concentration in blood	Searching for a biological sign of adrenal insufficiency : hyponatremia	Month 2
Measure of blood pressure	Searching for a clinical sign of adrenal insufficiency : low blood pressure	Month 1
Measure of blood pressure	Searching for a clinical sign of adrenal insufficiency : low blood pressure	Month 2
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
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
Measure of Weight	Evaluating if low body mass index increases clobetasol absorption and/or predicts adrenal insufficiency	Month 1
Measure of Weight	Evaluating if low body mass index increases clobetasol absorption and/or predicts adrenal insufficiency	Month 2
Measure of Height	Evaluating if low body mass index increases clobetasol absorption and/or predicts adrenal insufficiency	Month 1
Measure of Height	Evaluating if low body mass index increases clobetasol absorption and/or predicts adrenal insufficiency	Month 2
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
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

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Anne Pham-Ledard, MD, PhD, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: November 17, 2023
• First Submitted That Met QC Criteria: November 17, 2023
• First Posted (Actual): November 28, 2023

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Adrenal insufficiency; Topical corticosteroids; Bullous Pemphigoid; Iatrogenic
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Skin Diseases, Vesiculobullous; Adrenal Gland Diseases; Pemphigoid, Bullous; Adrenal Insufficiency; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Clobetasol
• Other Study ID Numbers: CHUBX 2023/07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No