Fetal Hemoglobin Induction Treatment Metformin (FITMet)

• ClinicalTrials.gov Identifier: NCT02981329
• Recruitment Status: Completed
• First Posted: December 5, 2016
• Last Update Posted: February 21, 2023
• Sponsor: Baylor College of Medicine
• Collaborator: Pfizer
• Information provided by (Responsible Party): Titilope Fasipe, Baylor College of Medicine

Tracking Information

• First Submitted Date: December 1, 2016
• First Posted Date: December 5, 2016
• Last Update Posted Date: February 21, 2023
• Actual Study Start Date: March 2, 2017
• Actual Primary Completion Date: July 20, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 17, 2020)

Change in Fetal Hemoglobin (HbF) Percentage (SCA) or Change in Total Hemoglobin (Hb) [ Time Frame: 1 Year ]

Change in HbF percentage (%) or total Hb will be assessed by comparing baseline values to on treatment values per subject and will be summarized.

Original Primary Outcome Measures (submitted: December 2, 2016)

Change in Fetal Hemoglobin (HbF) Percentage (SCA) or Change in Total Hemoglobin (Hb) (NTDT) [ Time Frame: 1 Year ]

Change in HbF percentage (%) or total Hb will be assessed by comparing baseline values to on treatment values per subject and will be summarized.

Current Secondary Outcome Measures (submitted: August 29, 2019)

• Change in Laboratory Values [ Time Frame: 1 Year ]
  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.
• Impact on Quality of Life [ Time Frame: 1 Year ]
  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.
• Variability of Hemoglobin Response [ Time Frame: 1 Year ]
  Evaluation of hematological variability of fetal hemoglobin induction will be assessed per subject per genetic analysis and summarized.
• Evaluation of RNA Sequencing [ Time Frame: 1 Year ]
  Evaluate expression changes in paired samples collected before and on metformin through RNA sequencing.

Original Secondary Outcome Measures (submitted: December 2, 2016)

• Change in Laboratory Values [ Time Frame: 1 Year ]
  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.
• Impact on Quality of Life [ Time Frame: 1 Year ]
  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.
• Variability of Hemoglobin Response [ Time Frame: 1 Year ]
  Evaluation of hematological variability of fetal hemoglobin induction will be assessed per subject per genetic analysis and summarized.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Fetal Hemoglobin Induction Treatment Metformin
• Official Title: Use of Metformin as a Fetal Hemoglobin Inducer in Patients With Hemoglobinopathies
• Brief Summary: The purpose of this study is to determine whether metformin is effective in the treatment for sickle cell anemia (SCA).
• 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
• Study Phase: Early Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Sickle Cell Anemia
• Sickle Cell Disease
• Hemoglobin Disorder

Intervention

• 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

Study Arms

• Experimental: Group A: Hydroxyurea + Metformin
  Subjects who are currently taking Hydroxyurea as part of standard of care and have sickle cell anemia.
  Interventions:

  • Drug: Metformin
  • Behavioral: Questionnaires
• 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.
  Interventions:

  • Drug: Metformin
  • Behavioral: Questionnaires

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 2, 2016): 37
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: July 20, 2020
• Actual Primary Completion Date: July 20, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years to 60 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02981329
• Other Study ID Numbers: H-38457 Metformin
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.

• Current Responsible Party: Titilope Fasipe, Baylor College of Medicine
• Original Responsible Party: Vivien Sheehan, Baylor College of Medicine, Assistant Professor
• Current Study Sponsor: Baylor College of Medicine
• Original Study Sponsor: Same as current
• Collaborators: Pfizer

Investigators

• Principal Investigator: Titilope Fasipe, MD; Baylor College of Medicine

• PRS Account: Baylor College of Medicine
• Verification Date: February 2023