Quercetin in Patients With XIAP (X-linked Inhibitor of Apoptosis) Deficiency

A Pilot Study to Evaluate Safety and Tolerability, Pharmacokinetics, and Preliminary Efficacy of Quercetin in Patients With XIAP (X-linked Inhibitor of Apoptosis) Deficiency

The purpose of the study is to evaluate safety and tolerability of oral quercetin in reducing inflammation in male patients with XIAP deficiency. Quercetin is a naturally occurring antioxidant that has many properties including the ability to decrease inflammation in other diseases.

Study Overview

• Status: Recruiting
• Conditions: XIAP Deficiency
• Intervention / Treatment: Drug: Quercetin

Detailed Description

XIAP deficiency is a rare genetic immune disorder. XIAP usually suppresses inflammation and XIAP deficiency leads to increased inflammation. Patients may develop several inflammatory problems including hemophagocytic lymphohistiocytosis (HLH), a life-threatening syndrome of overwhelming inflammation characterized by fever, low blood counts (cytopenias), an enlarged spleen, liver problems, seizures, and other manifestations. Patients may develop milder symptoms such recurrent fevers or problems with low blood counts. Inflammatory bowel disease (IBD), arthritis or inflammation of the eyes (uveitis) can also occur, among other more rare complications. XIAP deficiency is often life-threatening and patients with severe disease require treatment with allogeneic hematopoietic cell transplantation (HCT), which is the only available curative treatment. Unfortunately, allogeneic HCT is associated with a high risk of mortality and significant side effects. Therefore, it's important to find other treatment options that are safe without major side effects.

The purpose of the study is to evaluate safety and tolerability of oral quercetin in reducing inflammation in male patients with XIAP deficiency. Quercetin is a naturally occurring antioxidant that has many properties including the ability to decrease inflammation in other diseases.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Richard Cooper; Phone Number: 513-803-7450; Email: richard.cooper@cchmc.org
• Study Contact Backup: Name: Kelly McIntosh; Phone Number: 513-803-0460; Email: Kelly.McIntosh@cchmc.org

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
      • Contact: Richard Cooper; Phone Number: 513-803-7450; Email: richard.cooper@cchmc.org
      • Principal Investigator: Rebecca Marsh, MD
      • Contact: Kelly McIntosh; Phone Number: 513-803-0460; Email: Kelly.McIntosh@cchmc.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male patients
• Diagnosis of XIAP deficiency
• Patients ≥2 years of age
• Serum IL-18 ≥600 pg/mL (approximately 25% above the lab-defined upper limit of normal of 477 pg/mL)
• Able to take enteral medication

Exclusion Criteria:

• Renal failure requiring dialysis
• Total bilirubin >3 mg/dl and/or SGPT >300 at time of enrollment
• Patients receiving digoxin therapy, who are unable to discontinue treatment due to medical reasons
• Patients receiving fluoroquinolone therapy, who are unable to discontinue treatment due to medical reasons
• Patients who are at risk of pregnancy or fathering a child and are unable to use acceptable methods of birth control during the length of the study
• Patients who have received quercetin or any over the counter anti-oxidant supplementation within last 1 month
• Patients with unstable disease status or other medical issues requiring hospitalization or rapid escalation of medical care
• Participating in another therapeutic study for XIAP deficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Quercetin; All subjects will receive a weight adjusted dose of quercetin for a maximum total daily dose of 4000mg/day, divided twice a day.	Drug: Quercetin; Quercetin will be administered orally at a weight adjusted dose for a maximum total daily dose of 4000mg/day, divided twice a day. If the patient is 70 kg or more, the dose will automatically be assigned at the maximum dose of 4000mg/day. Patients will be instructed to mix quercetin with a small amount of yogurt or other preferred food for ingestion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of quercetin in patients with XIAP deficiency	Assessment of AEs	6 months
Tolerability of quercetin in patients with XIAP deficiency	Number of subjects who discontinue study drug due to intolerance	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) of quercetin in patients with XIAP deficiency	'Area under the curve (AUC)' will be utilized to describe PK of quercetin in these patients	Pre and post dose at baseline, 2 months, and 6 months

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Rebecca Marsh, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: February 20, 2026
• First Submitted That Met QC Criteria: February 20, 2026
• First Posted (Actual): February 25, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lymphoproliferative Syndrome, X-Linked, 2; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrans; Benzopyrans; Flavonols; Flavonoids; Chromones; Quercetin
• Other Study ID Numbers: 2024-0601

Drug and device information, study documents

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