Fetal Hemoglobin Induction Treatment Metformin

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

Detailed Description
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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.

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

Conditions
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Sickle Cell Anemia, Sickle Cell Disease, Hemoglobin Disorder

Intervention / Treatment
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* Drug: Metformin
* Behavioral: Questionnaires


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of sickle cell anemia Age greater than or equal to 10 and less than or equal to 60 years of age. 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. Creatinine less than or equal to 1.4 mg/dL and estimated glomerular filtration rate greater than 45 ml/min/1.73 m2 Liver function tests (specifically ALT and conjugated bilirubin) less than or equal to 4 times upper limits of normal. Exclusion Criteria: Failure to meet inclusion criteria Simple or chronic red blood cell transfusion therapy in the last 3 months OR a HbA level greater than 5% in SCA patients Refusal to use medically effective birth control if female and sexually active. If on hydroxyurea, not at stable dose of hydroxyurea for a minimum of 4 months (temporary exclusion). Creatinine greater than 1.4mg/dL Liver function tests (ALT and conjugated bilirubin) greater than 4 times upper limits of normal.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin, Sickle Cell Anemia, Sickle Cell Disease, Hemoglobinopathies, Hemoglobin Disorder, Blood Disease, Hemoglobin Disease