Identification of Anti-HIF 1alpha Autoantibodies in Patients With Anorexia Nervosa and Characterization of Their Pathogenic Potential in Undernutrition-associated Hepatic Cytolysis (HIAM)

March 11, 2026 updated by: Assistance Publique Hopitaux De Marseille

Anorexia nervosa (AN) is a psychiatric disorder belonging to the eating disorders (EDs). It is internationally recognized as a priority for improving health care. Among the markers of severity of undernutrition is hepatic cytolysis. Around 30-50% of patients with AN present with hepatic cytolysis, of variable intensity, and usually associated with severe undernutrition. In a previous study, we demonstrated the presence of autoantibodies against HIF1alpha (Hypoxic inducible Factor 1 alpha) in 22% of cases in a sample of patients with AN. HIF1alpha (HIF1a) is a major transcription factor involved in the regulation of satiety and hunger. These autoantibodies were positive in 80% of AN patients with hepatic cytolysis. Taken together, these data led us to hypothesize an anti-HIF1a autoimmune mechanism in AN, potentially involved in the patients' hepatic cytolysis.

This pioneering study, demonstrating the existence of anti-HIF1a autoantibodies, was carried out on a population of 18 patients with AN. To extend investigator's hypothesis, these results need to be confirmed on a larger number of patients, thus increasing the number of patients with AN and hepatic cytolysis. To determine the relevance of these autoantibodies in AN, "healthy" subjects and patients without AN but with hepatic cytolysis should be tested in parallel. Finally, the in vitro pathogenic potential of autoantibodies can be confirmed on a larger scale and studied in greater detail.

The main aim of our study is to evaluate the association between the presence of anti-HIF1a autoantibodies (AAHIF) and that of hepatic cytolysis in patients with anorexia nervosa and undernutrition.

This study is a prospective, cross-sectional, descriptive, multicenter, 2-arm study.

250 patients will be included. Experimental group (n=100)

  • Patients with anorexia nervosa and undernutrition with hepatic cytolysis (CH) (n=70)
  • Patients with anorexia nervosa and undernutrition without hepatic cytolysis (n=30) Comparator control groups (n=150)
  • Control patients under 18 years of age, treated at the CHU de la Timone for scheduled non-inflammatory surgery (orthopedic, ENT, etc.) (n=50): Minor patients
  • Patients (children and adults) with hepatic cytolysis without anorexia nervosa (n=50): Patients without AN with CH
  • Samples from French blood donation establishment: control group consisting of biological blood samples from healthy individuals from the Etablissement Français du Sang (n=50)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

250

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Marseille, France, 13005
        • Recruiting
        • Assistance Publique Hopitaux de Marseille
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Experimental group:

  • Male or female, 6 to 65 years of age
  • Anorexia nervosa diagnosed according to DSM-5 criteria
  • Presence of undernutrition according to HAS 2019 criteria
  • Patient having received information about the study and having signed an informed consent form
  • Beneficiary or beneficiary of a social security scheme

Control group:

  • Minor patients :

    • Male or female strictly under 18 years of age
    • Patients undergoing scheduled non-inflammatory surgery (orthopedic, ENT, etc.)
    • Patients who have been informed about the study and have signed an informed consent form.
    • Patients who are beneficiaries or entitled beneficiaries of a social security scheme.

  • Patients without anorexia with livers cytolysis :

    • Male or female between 18 and 65 years of age
    • With hepatic cytolysis determined by an ALT value at least equal to twice the normal value
    • Patient having received information about the study and having signed an informed consent form
    • Patient who is a beneficiary or eligible beneficiary of a social security scheme.
  • samples Etablissement Français de don de sang: no specific criteria

Exclusion Criteria:

  • Patient in a period of exclusion from another research protocol at the time consent is signed.
  • Opposition of patient and parents or legal guardians
  • Psychiatric disorder preventing patient consent to study
  • Person unable to understand the French language
  • Subjects covered by articles L1121-5 to 1121-8 of the French Public Health Code (minors, adults under guardianship or trusteeship, patients deprived of their liberty, pregnant or breast-feeding women).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patient with anorexia nervosa and anti-HIF1a autoantibody positivity
When blood is drawn as part of the treatment, three additional dry tubes will be taken for the immunology laboratory (see study diagram). These three dry tubes will be used to test for 1/ anti-nuclear autoantibodies and those associated with hepatic autoimmune pathologies 2/ AAHIF and assess their pathogenic potential using techniques already developed. In the event of AAHIF positivity, a second sample will be taken between 12 and 16 weeks later to verify the persistence of autoantibodies: Visit 2. The third dry tube will be sent to the Biogénopole Biological Resource Center (CHU Timone, APHM).
Other: blood sampling
When blood is drawn as part of the treatment, three additional dry tubes will be taken for the immunology laboratory (see study diagram). These three dry tubes will be used to test for 1/ anti-nuclear autoantibodies and those associated with hepatic autoimmune pathologies 2/ AAHIF and assess their pathogenic potential using techniques already developed. The third dry tube will be sent to the Biogénopole Biological Resource Center (CHU Timone, APHM).
Other: blood sampling after 3-4 months
In the event of AAHIF positivity, a second sample will be taken between 12 and 16 weeks later to verify the persistence of autoantibodies: Visit 2.
Experimental: Patient with anorexia nervosa and no anti-HIF1a autoantibody positivity
When blood is drawn as part of the treatment, three additional dry tubes will be taken for the immunology laboratory (see study diagram). These three dry tubes will be used to test for 1/ anti-nuclear autoantibodies and those associated with hepatic autoimmune pathologies 2/ AAHIF and assess their pathogenic potential using techniques already developed. The third dry tube will be sent to the Biogénopole Biological Resource Center (CHU Timone, APHM).
Other: blood sampling
When blood is drawn as part of the treatment, three additional dry tubes will be taken for the immunology laboratory (see study diagram). These three dry tubes will be used to test for 1/ anti-nuclear autoantibodies and those associated with hepatic autoimmune pathologies 2/ AAHIF and assess their pathogenic potential using techniques already developed. The third dry tube will be sent to the Biogénopole Biological Resource Center (CHU Timone, APHM).
Active Comparator: Patient without anorexia nervosa and anti-HIF1a autoantibody positivity
When blood is drawn as part of the treatment, three additional dry tubes will be taken for the immunology laboratory (see study diagram). These three dry tubes will be used to test for 1/ anti-nuclear autoantibodies and those associated with hepatic autoimmune pathologies 2/ AAHIF and assess their pathogenic potential using techniques already developed. In the event of AAHIF positivity, a second sample will be taken between 12 and 16 weeks later to verify the persistence of autoantibodies: Visit 2. The third dry tube will be sent to the Biogénopole Biological Resource Center (CHU Timone, APHM).
Other: blood sampling
When blood is drawn as part of the treatment, three additional dry tubes will be taken for the immunology laboratory (see study diagram). These three dry tubes will be used to test for 1/ anti-nuclear autoantibodies and those associated with hepatic autoimmune pathologies 2/ AAHIF and assess their pathogenic potential using techniques already developed. The third dry tube will be sent to the Biogénopole Biological Resource Center (CHU Timone, APHM).
Other: blood sampling after 3-4 months
In the event of AAHIF positivity, a second sample will be taken between 12 and 16 weeks later to verify the persistence of autoantibodies: Visit 2.
Active Comparator: Patient without anorexia nervosa and no anti-HIF1a autoantibody positivity
When blood is drawn as part of the treatment, three additional dry tubes will be taken for the immunology laboratory (see study diagram). These three dry tubes will be used to test for 1/ anti-nuclear autoantibodies and those associated with hepatic autoimmune pathologies 2/ AAHIF and assess their pathogenic potential using techniques already developed. The third dry tube will be sent to the Biogénopole Biological Resource Center (CHU Timone, APHM).
Other: blood sampling
When blood is drawn as part of the treatment, three additional dry tubes will be taken for the immunology laboratory (see study diagram). These three dry tubes will be used to test for 1/ anti-nuclear autoantibodies and those associated with hepatic autoimmune pathologies 2/ AAHIF and assess their pathogenic potential using techniques already developed. The third dry tube will be sent to the Biogénopole Biological Resource Center (CHU Timone, APHM).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of anti-HIF1a autoantibodies (AAHIF) in comparison with the presence of hepatic cytolysis in patients with anorexia nervosa and undernutrition
Time Frame: From enrollment to the end of study at 36 months
Comparison of the prevalence of anti-HIF1a autoantibodies (AAHIF) in patients with AM according to the presence or absence of hepatic cytolysis.
From enrollment to the end of study at 36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of AAHIF in a population of healthy subjects
Time Frame: From enrollment to the end of the study at 36 months
From enrollment to the end of the study at 36 months
Rate of AAHIF in patients without anorexia nervosa and with hepatic cytolysis.
Time Frame: From enrollment to the end of the study at 36 months
From enrollment to the end of the study at 36 months
Rate of AAHIF in patients with anorexia nervosa and suffering from malnutrition
Time Frame: From enrollment to the end of the study at 36 months
From enrollment to the end of the study at 36 months
Rate of AAHIF according to clinico-biological criteria for AOS identified in routine care
Time Frame: From enrollment to the end of the study at 36 months
age, sex, type of AN (pure or mixed restrictive, restrictive and hyperphagic/purgative), duration of disorders, attitudes and behaviors related to AN (assessed by the Eating Disorder Inventory 2 EDI 2 questionnaire), weight, BMI, weight loss in 1 month, weight loss in 6 months or since onset of illness, severity of undernutrition, presence of problematic physical hyperactivity (assessed by the Exercise Dependence Scale-Revised EDSR questionnaire), presence of amenorrhea, use of enteral nutrition, associated treatments, leukocytes, neutrophils, lymphocytes, hemoglobin, platelets, creatinine, urea, AST, ALT, GGT, fasting blood glucose, PT, albumin, pre-albumin (transthyretin), vitamin B12, folate, vitamin D, ferritin.
From enrollment to the end of the study at 36 months
Pathogenic potential in vitro of AAHIF in hepatic cytolysis
Time Frame: From enrollment to the end of the study at 36 months
Functional effects of the purified AAHIF fraction on hepatocyte cell lysis and its impact on HIF1a-dependent signaling.
From enrollment to the end of the study at 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique Hopitaux De Marseille

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 2, 2026

Primary Completion (Estimated)

May 24, 2027

Study Completion (Estimated)

May 24, 2029

Study Registration Dates

First Submitted

February 26, 2025

First Submitted That Met QC Criteria

March 5, 2025

First Posted (Actual)

March 11, 2025

Study Record Updates

Last Update Posted (Actual)

March 13, 2026

Last Update Submitted That Met QC Criteria

March 11, 2026

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RCAPHM24_0497
  • 2025-A00018-41 (Other Identifier: IDRCB)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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