Fetal Hemoglobin Induction Treatment Metformin (FITMet)

Use of Metformin as a Fetal Hemoglobin Inducer in Patients With Hemoglobinopathies

The purpose of this study is to determine whether metformin is effective in the treatment for sickle cell anemia (SCA).

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease; Sickle Cell Anemia; Hemoglobin Disorder
• Intervention / Treatment: Drug: Metformin; Behavioral: Questionnaires

Detailed Description

This is a dose escalation, pilot study for subjects with sickle cell anemia (SCA) disease to determine if metformin has a beneficial effect on the treatment and quality of life of SCA patients.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Confirmed diagnosis of sickle cell anemia
2. Age greater than or equal to 10 and less than or equal to 60 years of age.
3. If on hydroxyurea, fetal hemoglobin less than 20% at a stable dose (mg/kg) determined by the primary hematology provider over at least four months.
4. Creatinine less than or equal to 1.4 mg/dL and estimated glomerular filtration rate greater than 45 ml/min/1.73 m2
5. Liver function tests (specifically ALT and conjugated bilirubin) less than or equal to 4 times upper limits of normal.

Exclusion Criteria:

1. Failure to meet inclusion criteria
2. Simple or chronic red blood cell transfusion therapy in the last 3 months OR a HbA level greater than 5% in SCA patients
3. Refusal to use medically effective birth control if female and sexually active.
4. If on hydroxyurea, not at stable dose of hydroxyurea for a minimum of 4 months (temporary exclusion).
5. Creatinine greater than 1.4mg/dL
6. Liver function tests (ALT and conjugated bilirubin) greater than 4 times upper limits of normal.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Hydroxyurea + Metformin; Subjects who are currently taking Hydroxyurea as part of standard of care and have sickle cell anemia.	Drug: Metformin; Metfomin will be taken daily. The metformin dose will be increased during two time points per subject if protocol dose escalation criteria is met.; Other Names: Glucophage; Riomet,; Behavioral: Questionnaires; Questionnaires will be completed to assess the impact quality of life
Experimental: Group B: Metformin (Group B has closed to enrollment); Subjects who are not taking Hydroxyurea as part of standard of care and have sickle cell anemia.	Drug: Metformin; Metfomin will be taken daily. The metformin dose will be increased during two time points per subject if protocol dose escalation criteria is met.; Other Names: Glucophage; Riomet,; Behavioral: Questionnaires; Questionnaires will be completed to assess the impact quality of life

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fetal Hemoglobin (HbF) Percentage (SCA) or Change in Total Hemoglobin (Hb)	Change in HbF percentage (%) or total Hb will be assessed by comparing baseline values to on treatment values per subject and will be summarized.	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Laboratory Values	Evaluation and percentage of change in numeric values of total blood count, liver function, HbF levels, whole blood viscosity, and percent dense red blood cells will be evaluated per subject over the duration of the study and summarized.	1 Year
Impact on Quality of Life	Evaluation of subject's change in quality of life will be assessed per subject per study questionnaire(s) over the duration of the study and summarized.	1 Year
Variability of Hemoglobin Response	Evaluation of hematological variability of fetal hemoglobin induction will be assessed per subject per genetic analysis and summarized.	1 Year
Evaluation of RNA Sequencing	Evaluate expression changes in paired samples collected before and on metformin through RNA sequencing.	1 Year

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: Pfizer
• Investigators: Principal Investigator: Titilope Fasipe, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2017
• Primary Completion (Actual): July 20, 2020
• Study Completion (Actual): July 20, 2020

Study Registration Dates

• First Submitted: December 1, 2016
• First Submitted That Met QC Criteria: December 2, 2016
• First Posted (Estimated): December 5, 2016

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Metformin; Sickle Cell Disease; Sickle Cell Anemia; Hemoglobinopathies; Hemoglobin Disorder; Blood Disease; Hemoglobin Disease
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia, Sickle Cell; Hemoglobinopathies; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: H-38457 Metformin

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The leftover blood samples for genetic analysis will be banked indefinitely for future ancillary studies. Investigator who desires access to these samples must present their research idea prior to receiving access to the samples. The samples will be shared with researchers affiliated with Texas Children's Hospital, Baylor College of Medicine and/or other hematology collaborators for future studies associated with hematologic diseases and drugs used to treat such diseases. The recipient investigators are required to provide proof of IRB approval or exemption as per local IRB guidelines before the sample can be released for research purposes. After receipt of IRB approval, coded samples will be distributed to the recipient investigator.

Drug and device information, study documents

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