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RecruitingNCT06519786Updated Jul 25, 2024

Safety and Efficacy of Metformin for Treatment of Cytopenia in Children and Adolescents With Fanconi Anemia

A Phase 3 interventional study of Metformin in Fanconi Anemia, sponsored by Ain Shams University. Recruiting at 2 sites in Egypt. Open to participants aged 5 Years to 18 Years. Per ClinicalTrials.gov, last updated 2024-07-25.

Sponsored by Ain Shams University · Phase 3, Interventional, and Supportive care

Phase
Phase 3
Study type
Interventional
Enrollment
30
Allocation
Non-randomized
Ages
5 Years to 18 Years
Sex
All
01

Study summary

Prospective interventional open-label non-randomized controlled trial to assess safety and efficacy of metformin in treating cytopenia in children and adolescents with Fanconi Anemia.

Read the detailed description

Fanconi anemia (FA) is a genetic disease characterized by bone marrow failure, cancer susceptibility, and developmental abnormalities. Allogeneic hematopoietic stem cell transplantation offers curative therapy for hematologic complications of FA.

Oxymetholone is commonly used in the management of FA as it improves blood counts, red cells, and platelets. However, its use is limited by its high toxicity profile.

Metformin is a potential agent that reduces levels of both chromosomal radials and breaks in FA cells and increases the size of the hematopoietic stem cell compartment thus reducing cytopenia in patients with FA.

02

Conditions studied

03

Who can participate

Ages eligible
5 Years to 18 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Age: 5 to 18 years
  • Patients who are diagnosed with Fanconi anemia based on clinical features and confirmed by increased chromosomal breakage on diepoxybutane (DEB) stress testing.
  • Presence of cytopenia (at least one of the following: hemoglobin (Hb) \< 10 g/dL, platelet count \< 100 x 109/L, or an absolute neutrophil count (ANC) \< 1.0 x 109/L
  • Patients receiving other therapies e.g., androgens are eligible for enrollment after a one-month washout period before the start of metformin.

Exclusion criteria

Exclusion Criteria:

  • Patients who underwent bone marrow transplantation.
  • Patients with evidence of myelodysplasia, leukemia, or other concurrent malignancy.
  • Patients who have a history of allergic reactions to metformin or similar compounds.
  • Patients with a history of symptomatic hypoglycemia over the past year or hypoglycemia \< 50 mg/dL on screening and baseline laboratory assessments.
  • Patients with type 1 diabetes mellitus.
  • Patients with vitamin B12 deficiency.
  • Patients with Glucose-6-Phosphate Dehydrogenase deficiency.
  • Patients with abnormal Kidney function tests including serum creatinine, elevated liver function tests including live enzymes (ALT or AST > 135 U/L, total bilirubin > 1.5 x upper limit of normal for age, and/or patients with metabolic acidosis (bicarbonate \< 17 meq/L on venous blood gases).
04

Study design

Phase
Phase 3
Primary purpose
Supportive care
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
30 participants (estimated)

Study arms

  • Experimental
    Metformin group

    Patients will receive metformin immediate-release tablets orally for 24 weeks. Starting dose will be 500 mg once daily for all patients and the dose will be increased by 500 mg weekly until the goal dose is achieved (500 mg twice daily for patients \< 10 years of age, and 1000 mg twice daily for patients 10 years or older).

    Drug: Metformin

  • No intervention
    Other treatment group

    Patients will receive supportive treatment as indicated

Interventions

  • DrugMetformin

    Patients will receive metformin immediate-release tablets orally for 24 weeks. Starting dose will be 500 mg once daily for all patients and the dose will be increased by 500 mg weekly until the goal dose is achieved (500 mg twice daily for patients \< 10 years of age, and 1000 mg twice daily for patients 10 years or older)

    Also known as: Glucophage

05

What researchers measure

Primary outcomes

  1. Hematologic response (erythroid)

    Erythroid response (pretreatment, \< 11 g/dL): Hgb increase by \> 1.5 g/dL or Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk.

    Time frame: 24 weeks

  2. Hematologic response (platelets)

    Platelet response (pretreatment, \< 100x10e9/L): Absolute increase of \> 30 x 10e9/L for patients starting with \> 20 x 10e9/L platelets or Increase from \< 20 x 10e9/L to \> 20 x10e9/L and by at least 100%

    Time frame: 24 weeks

  3. Hematologic response (Neutrophil count)

    Neutrophil response (pretreatment, \< 1.0 x 10e9/L): At least 100% increase and an absolute increase \> 0.5 x 10e9/L

    Time frame: 24 weeks

06

Study locations

2 of 2 sites recruiting
  • University of Alexandria
    Alexandria, Egypt
    Recruiting
  • Ain Shams University
    Cairo, 11566, Egypt
    Recruiting
07

Registry details

Key details

Study ID
NCT06519786
Lead sponsor
Ain Shams University
Responsible party
Sponsor
First posted
Jul 25, 2024
Start date
Oct 5, 2022
Primary completion
Oct 2024 (estimated)
Completion
Mar 2025 (estimated)
Last update
Jul 25, 2024

Study contacts

Sara M Makkeyah, MD
Contact
smakkeyah@med.asu.edu.eg
+201140105222

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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