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Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid

This study is not yet open for participant recruitment.
Verified April 2013 by Centre Hospitalier Universitaire de Nīmes
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier:
NCT01559155
First received: March 19, 2012
Last updated: April 25, 2013
Last verified: April 2013
History of Changes
  Purpose

The primary objective of this study is to describe and compare plasmatic anti-proteasome auto-antibody concentrations among three distinct groups: (1) patients suffering from bullous pemphigoide; (2) patients suffering from other dermatological auto-immune diseases; (3) an elderly control group.


Condition
Pemphigoid, Bullous
Pemphigus
Lupus Erythematosus, Cutaneous

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Centre Hospitalier Universitaire de Nīmes:

Primary Outcome Measures:
  • Plasmatic concentration of anti-proteasome autoantibodies (ng/ml) [ Time Frame: baseline ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • the daily number of new lesions [ Time Frame: baseline ] [ Designated as safety issue: No ]
    For patients suffering from bullous pemphigoid or pemphigus: the daily number of new lesions for the 3 days preceding blood sampling

  • Presence/absence of mucosal disease [ Time Frame: baseline ] [ Designated as safety issue: No ]
    For patients suffering from bullous pemphigoid only

  • Disease duration (weeks) [ Time Frame: baseline ] [ Designated as safety issue: No ]
    For patients suffering from bullous pemphigoid or pemphigus or lupus

  • % surface area [ Time Frame: baseline ] [ Designated as safety issue: No ]
    For patients suffering from bullous pemphigoid or pemphigus or lupus: % of skin area affected in relation to total area

  • Puritis score [ Time Frame: baseline ] [ Designated as safety issue: No ]
    For patients suffering from bullous pemphigoid only: severity of itching on a analog scale varying from 0 to 6

  • concentration of anti-PB18 antibodies, measured by ELISA [ Time Frame: baseline ] [ Designated as safety issue: No ]
    For patients suffering from bullous pemphigoid only; U/ml

  • Immunohistochemistry [ Time Frame: baseline ] [ Designated as safety issue: No ]
    For the first 10 patients suffering from bullous pemphigoid included at the Nîmes University Hospital only; Skin biopsy immunohistochemistry scores for the pan-alpha, alpha6, beta1, beta2, beta1i, beta5i and rpt5 subunits (negative, weak, moderate, strong)

  • Tissue DNA expression [ Time Frame: baseline ] [ Designated as safety issue: No ]
    For the first 10 patients suffering from bullous pemphigoid included at the Nîmes University Hospital only; Skin biopsy, plasma and circulating mononuclear cell DNA expression for the pan-alpha, alpha6, beta1, beta2, beta1i, beta5i and rpt5 subunits (weighted by beta-actin)

  • presence/absence of oral lesions [ Time Frame: baseline ] [ Designated as safety issue: No ]
    For patients suffering from pemphigus

  • Presence/absence of Nikolsky's sign [ Time Frame: baseline ] [ Designated as safety issue: No ]
    For patients with pemphigus only

  • Pemphigus disease area index [ Time Frame: baseline ] [ Designated as safety issue: No ]
    For patients with Pemphigus only; score varying from 0 to 120.

  • Anti-desmogleine 1 and 3 antibody concentrations [ Time Frame: baseline ] [ Designated as safety issue: No ]
    For patients with Pemphigus only; ELISA (U/ml

  • CLASI score for lupus [ Time Frame: baseline ] [ Designated as safety issue: No ]
    for lupus patients only; score varying from 0 to 70

  • Karnofsky's score (%) [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Plasma proteasome concentration [ Time Frame: baseline ] [ Designated as safety issue: No ]
    ng/ml

  • % trypsin-like plasma proteasome proteolytic activity [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • % chymotrypsin-like plasma proteasome proteolytic activity [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • % caspase-like plasma proteasome proteolytic activity [ Time Frame: baseline ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

All left over plasma samples will be incorporated into the biological collection at the Nîmes University Hospital.


Estimated Enrollment: 130
Study Start Date: May 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Bullous pemphigoid
Patients in this cohort are newly diagnosed (or have not started treatment) with bullous pemphigoid
Other bullous-like auto-immune
Patients in this cohort are newly diagnosed (or have not started treatment) with pemphigus (15 patients) or cutaneous lupus (15 patients)
Control group
Patients in this cohort are hospitalized at the Nîmes University Hospital, and have no history of autoimmune, inflammatory or neoplastic disease. Patients are matched for age and sex with patients in the bullous pemphigoid cohort.

Detailed Description:

The secondary objectives of this study are:

To compare the following parameters between the 3 groups:

  • plasmatic proteasome concentrations
  • plasmatic proteasome proteolytic activity

To explore the potential relationships between:

  • plasmatic proteasome concentrations
  • plasmatic proteasome proteolytic activity
  • plasmatic anti-proteasome auto-antibody concentrations
  • measures of disease severity for dermatological auto-immune diseases

To characterize plasmatic anti-proteasome auto-antibodies in patients suffering from bullous pemphigoide and other dermatological auto-immune diseases (other bullous auto immune diseases: pemphigus, cutaneous lupus, ...).

To characterize the expression and the activity of proteasomes in skin samples, in plasma and in circulating mononuclear cells in patients with bullous pemphigoide.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

The study population is composed of three groups: (1) 50 patients with newly diagnosed (untreated) bullous pemphigoid, (2) 50 control patients matched for age and sex with the previous group and (3) 30 patients with other dermatological auto-immune disease (15 pemphigus + 15 cutaneous lupus).

Criteria

Inclusion Criteria:

  • The patient must have given his/her informed and signed consent
  • The patient must be insured or beneficiary of a health insurance plan

For the bullous pemphigoid group:

  • clinical signs: erythematous-based lesions, especially on flexion areas of the arms and legs, not afflicting mucous membranes, and without atrophic scaring
  • histology: without epidermal acantholysis
  • patient has not started treatment

For the pemphigus group:

  • patient with pemphigus
  • patient has not started treatment

For the lupus group:

  • systemic lupus patients: presence of the 4 diagnostic criteria for systemic lupus erythematosus as defined by the American College of Rheumatology (amended 1997)
  • or characteristics of subacute cutaneous lupus: clinical, histological and immunological (anti-SSa)
  • or clinical and histological characteristics of chronic lupus
  • the patient has not started treatment

For the control group:

  • hospitalized patients with no history of auto-immune, inflammatory or evolving neoplastic disease

Exclusion Criteria:

  • The patient is participating in another study
  • The patient is in an exclusion period determined by a previous study
  • The patient is under judicial protection, under tutorship or curatorship
  • The patient refuses to sign the consent
  • It is impossible to correctly inform the patient
  • The patient is pregnant, parturient, or breastfeeding

For patients with bullous pemphigoid, pemphigus or lupus:

  • the patient has started treatment for his/her autoimmune disease

For the controls:

  • autoimmune disease
  • inflammatory disease
  • evolving neoplastic disease
  • surgery during the last 6 months
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01559155

Contacts
Contact: Pierre Stoebner, MD +33.(0)4.66.68.40.43 pierre.stoebner@chu-nimes.fr
Contact: Carey M Suehs, Ph D +33.(0)4.66.68.67.88 carey.suehs@chu-nimes.fr

Locations
France
CHU de Nîmes - Hôpital Universitaire Carémeau
Nîmes Cedex 09, France, 30029
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nīmes
Investigators
Principal Investigator: Pierre Stoebner, MD Centre Hospitalier Universitaire de Nîmes
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier: NCT01559155     History of Changes
Other Study ID Numbers: LOCAL/2011/PS-02, 2012-A00180-43
Study First Received: March 19, 2012
Last Updated: April 25, 2013
Health Authority: France: Committee for the Protection of Personnes
France: L’Agence nationale de sécurité du médicament et des produits de santé

Keywords provided by Centre Hospitalier Universitaire de Nīmes:
proteasomes
proteasome concentration
disease activity
 proteolytic activity
autoantibodies
proteasome autoantibody

Additional relevant MeSH terms:
Autoimmune Diseases
Lupus Erythematosus, Cutaneous
Pemphigoid, Bullous
Pemphigus
Lupus Erythematosus, Systemic
 Immune System Diseases
Connective Tissue Diseases
Skin Diseases
Skin Diseases, Vesiculobullous

ClinicalTrials.gov processed this record on May 21, 2013