Quercetin in Children With Fanconi Anemia; a Pilot Study

Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone marrow failure (BMF), congenital abnormalities and a predisposition to malignancy.

Study Overview

• Status: Completed
• Conditions: Fanconi Anemia
• Intervention / Treatment: Drug: Quercetin (dietary supplement)

Detailed Description

Current therapies for children with Fanconi anemia (FA) and bone marrow failure, i.e. androgens or bone marrow transplantation, are associated with significant morbidity and mortality.

This is a pilot study aiming to assess feasibility, toxicity and pharmacokinetics of oral Quercetin therapy in patients with FA. This is a first step towards a clinical study of the efficacy of Quercetin therapy in delaying progression of BMF in FA.

Additional correlative studies will include assessment of impact of Quercetin on reduction of Reactive Oxygen Species (ROS), maintenance or improvement of hematopoietic stem cell (HSC) reserve, improvement of hematopoiesis (i.e. peripheral counts) and insulin sensitivity/glucose tolerance.

This study is an open-label single arm study.

Funding Source - FDA OOPD

Accrual closed for the main study. Expansion cohort added to observe additional patients at the desired dose.

Expansion Cohort:

The second and third cohort of participants completed the study treatment as expected, tolerating Quercetin well without any DLT. Based on the PK and ROS analyses, the dose was increased for the fourth cohort (subjects #10-12). To observe additional patients at the desired dose, an expansion cohort is being added. Up to 20 patients will be enrolled in the expansion cohort. The purpose of the expansion cohort is to assess the effects of quercetin supplement at the desired dose on clinical and biological endpoints.

Patients in the expansion cohort will receive quercetin treatment for the first 26 weeks. Patients will be able to continue quercetin supplement after the completion of the study period of 26 weeks if they wish. If patients decide to continue quercetin after the first 26 weeks, quercetin will be provided by the investigational pharmacy for up to 1 year. Patients who continue quercetin supplement after 26 weeks, but discontinue quercetin before 1 year will be followed through the 1 year visit. Patients who discontinue quercetin supplement any time after the 1 year visit will be followed through the 2 year visit.

Patients previously enrolled in the initial phase of the study (cohorts 1-4) may be considered for enrollment on the expansion cohort of the study provided they meet all inclusion and exclusion criteria.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of FA proven by DEB test or molecular testing
• Able to take enteral medication
• All age groups, including adults

Exclusion Criteria:

• Patients with morphological evidence of myelodysplasia or leukemia
• Renal failure requiring dialysis
• Total bilirubin > 3 mg/dl and/or SGPT >200 at time of enrollment
• Patients who are pregnant or breastfeeding or are at risk of pregnancy and are unable to use acceptable methods of birth control during the length of the study
• Patients receiving cyclosporine or digoxin therapy or are unable to discontinue either treatment due to medical reasons
• Patients who have received quercetin supplementation or other antioxidants within the last 30 days

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: Quercetin - Dietary Supplement; Quercetin will be given orally on a twice a day schedule starting with weight adjusted dose for a maximum total daily dose of 1500 mg/day, for 4 months (16 weeks). Pharmacokinetics (PK) data will be analyzed after each cohort of 3 patients and will be used to optimize the dosing schedule (if required) for subsequent patients. An expansion cohort has been added to the study protocol. Up to 20 patients may be enrolled. The dose utilized will be the same as the max weight adjusted dose that showed biological activity in our last cohort of patients (subjects #10-12 from above).

Drug: Quercetin (dietary supplement); Quercetin will be given orally on a twice a day schedule starting with weight adjusted dose for a maximum total daily dose of 1500 mg/day, for 4 months (16 weeks). Pharmacokinetics (PK) data will be analyzed after each cohort of 3 patients and will be used to optimize the dosing schedule (if required)for subsequent patients. An expansion cohort has been added to the study protocol. Up to 20 patients may be enrolled. The dose utilized will be the same as the max weight adjusted dose that showed biological activity in our last cohort of patients (subjects #10-12 from above).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Measure the ability to administer twice daily oral quercetin therapy in patients with Fanconi Anemia (FA).	4 months (16 weeks)
Measure safety of oral quercetin therapy in patients with FA	4 months (16 weeks)
To measure pharmacokinetics (PK) of oral quercetin therapy in patients with FA	4 months (16 weeks)

Secondary Outcome Measures

Outcome Measure	Time Frame
To measure the impact of quercetin therapy on reduction of Reactive Oxygen Species (ROS).	4 months (16 weeks) and 1 year
Number of participants with improved hematopoiesis.	4 months (16 weeks) and 1 year
Measure the preservation of hematopoietic stem cell reserve in patients with FA	4 months (16 weeks) and 1 year
To measure the impact of quercetin therapy on changes in insulin sensitivity/glucose tolerance.	4 month (16 weeks) and 1 year

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: Food and Drug Administration (FDA)
• Investigators: Principal Investigator: Parinda Mehta, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): October 26, 2021
• Study Completion (Actual): October 26, 2021

Study Registration Dates

• First Submitted: July 25, 2012
• First Submitted That Met QC Criteria: October 31, 2012
• First Posted (Estimated): November 2, 2012

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Fanconi Anemia; Quercetin; FA
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Bone Marrow Diseases; Hematologic Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Renal Tubular Transport, Inborn Errors; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia; Fanconi Syndrome; Fanconi Anemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants; Quercetin
• Other Study ID Numbers: 2011-2049; 1R01FD004383-01A1 (U.S. FDA Grant/Contract)

Plan for Individual participant data (IPD)

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