Effects of Hydroxyurea and Metformin in Transfusion Dependent Beta-Thalassemia

April 23, 2026 updated by: Ayesha Khan, Bahria University

This clinical trial aims to evaluate and compare the effects and safety of hydroxyurea and metformin in transfusion-dependent beta-thalassemia major and correlate responders/non-responders with the single nucleotide polymorphism mutations (SNPs) by DNA analysis.

The main question to answer is:

  • Is there a significant difference in the effects and safety of hydroxyurea and metformin in transfusion-dependent beta-thalassemia major?

Participants will be divided into two treatment groups. Participants of group A will receive Tab. Metformin 500mg/dose twice daily orally for one year. Participants of group B will receive Tab. Hydroxyurea 10-20mg/kg once daily orally for one year.

At the end of the study, Investigators will compare the effects and safety of hydroxyurea and metformin in transfusion-dependent beta-thalassemia major and correlate responders/non-responders with the single nucleotide polymorphism mutations (SNPs) by DNA analysis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study will be conducted after obtaining approval from the Institutional Review Board (IRB) at Bahria University Health Sciences Campus Karachi (BUHSCK) and the Faculty Research Committee (FRC). After obtaining written informed consent, 48 participants in each group with beta-thalassemia major will be selected from the National Institute of Blood Diseases and Bone Marrow Transplantation. Participants will be randomized into two treatment groups using computer-generated randomization.

Group A participants will receive Metformin 500 mg/dose twice daily orally for one year. Group B participants will receive Hydroxyurea 10-20 mg/kg once daily orally for one year.

Dose escalation therapy will be implemented to improve participant compliance and tolerance. The first month will not be included in the study period for each participant. A general physical examination will be conducted monthly. Blood pressure (mm Hg) will be assessed using a sphygmomanometer. The pulse rate (beats per minute) will be determined by palpating the radial artery, and the Body Mass Index (kg/m^2) will be calculated for each participant.

Dietary Counseling

People with thalassemia are advised to consume vitamin C-rich foods like vegetables and fruits to prevent depletion from iron overload. They should also include dairy products in their diet to counter calcium depletion, while avoiding high-iron foods such as beef, liver, spinach, and dates.

SF (Short-form) Questionnaire

All participants will complete the SF-36, a 36-item Short-Form Health Survey, at baseline, 6 months, and 12 months. The SF-36 is a widely used tool for evaluating overall health status, consisting of 36 items across 8 domains. The scores contribute to two main components: the physical component summary (PCS) and the mental component summary (MCS). The SF-36 is employed to assess Health-Related Quality of Life (HRQoL) in both the general population and individuals with various medical conditions, including beta-thalassemia major (β-TM), allowing for comparisons of HRQoL across different illnesses and health statuses.

I) Baseline Investigations/Parameters (at day zero)

Baseline investigations will include Complete Blood Count (CBC), Random Blood Sugar (RBS), Erythrocyte Sedimentation Rate (ESR), Serum Creatinine, Serum Ferritin, Liver Function Tests (LFTs), HCV RNA test, Fetal Hemoglobin (HbF) level, Abdominal Ultrasound, Dual-Energy X-ray Absorptiometry (DEXA) Scan, and DNA mutations. Health-Related Quality of Life (HRQoL) will be assessed by the SF-36 Questionnaire at baseline, 6 months, and 12 months.

II) Monthly Follow-up for Clinical Features

Only CBC will be performed monthly, and any adverse effects related to the drugs will be inquired about.

III) At 3 Months

CBC, RBS, Serum Creatinine, and LFTs will be assessed for any adverse effects on blood, kidneys, and liver.

IV) At 6 & 12 Months

All baseline investigations, except DNA mutations, will be repeated.

V) At 9 Months

Random Blood Sugar, Serum Ferritin, and Serum Creatinine will be assessed.

Adverse Effects of Drugs

Adverse effects will be explained to each participant as follows: A) Metformin: nausea, vomiting, abdominal bloating, diarrhea, etc. B) Hydroxyurea: cytopenia, nausea, vomiting, abdominal pain, rashes, etc.

DNA mutations will be analyzed using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) in responders and non-responders.

Data will be collected using the Consent Form and SF-36 Questionnaire. Data analysis will be performed using IBM Statistical Package for the Social Sciences (SPSS), version 27. A p-value ≤ 0.05 will be considered statistically significant. Descriptive statistics (mean ± SD) will be used for continuous variables, while categorical variables will be presented as frequencies and percentages. To determine the mean difference, a repeated-measures two-way ANOVA within each group will be used. For correlation analysis, an independent T-test will be employed.

Study Type

Interventional

Enrollment (Actual)

96

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Pakistan
    • Sindh
      • Karachi, Sindh, Pakistan
        • Bahria University Health Sciences Campus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosed cases of beta-thalassemia major
  • Transfusion dependent patients and on iron chelating agents
  • Males and females 10 to 25 years of age
  • Creatinine ≤1.4 mg/dL
  • Written informed consent from the patients and up to 18 years consent from the Parents/Guardians.

Exclusion Criteria:

  • Failure to meet inclusion criteria
  • Refusal to participate
  • Creatinine >1.4mg/dL
  • Liver function tests (ALT and conjugated bilirubin) > 4 times upper limits of normal
  • Massive splenomegaly & Liver fibrosis
  • Patient on growth hormone
  • Sickle beta thalassemia
  • Severe osteoporosis
  • Hepatitis B & C
  • HIV

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: (Group A) Tablet Metformin
Tablet Metformin 500 mg/dose orally twice a day with meal for 1 year
Drug: Tablet Metformin (Group A)
Tablet Metformin 500 mg/dose orally twice a day with meal for 1 year
Other Names:
  • Tab. Glucophage 500mg
Active Comparator: (Group B) Tablet Hydroxyurea
Tablet Hydroxyurea 10-20mg/kg once daily orally with breakfast for 1 year
Drug: Tablet Hydroxyurea (Group B)
Tablet Hydroxyurea 10-20mg/kg once daily orally with breakfast for 1 year
Other Names:
  • Cap. Hydrea 500mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Fetal Haemoglobin (HbF) Percentage in responders and non-responders
Time Frame: 6 months to 1 year after the baseline
Assessment will be done at 6 months and 1 year after the baseline
6 months to 1 year after the baseline
Change in frequency of blood transfusions
Time Frame: 6 months to 1 year after the baseline
Assessment will be done at 6 months and 1 year after the baseline
6 months to 1 year after the baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in quality of life assessed by the 36-Item Short Form Health Survey (SF-36) Questionnaire
Time Frame: 6 months to 1 year from the baseline
Assessment will be conducted on a scoring scale of 0 to 100, with 0 being the lowest and 100 the highest possible scores, at 6 months and 1 year after the baseline.
6 months to 1 year from the baseline
Correlations of responders and non-responders with DNA mutations
Time Frame: After 1 year at the end of study
Assessment will be done after 1 year from the baseline
After 1 year at the end of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bahria University

Investigators

  • Principal Investigator: Ayesha Khan, MBBS MPhil, Bahria University Islamabad

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 16, 2024

Primary Completion (Actual)

February 9, 2026

Study Completion (Actual)

February 9, 2026

Study Registration Dates

First Submitted

September 11, 2024

First Submitted That Met QC Criteria

September 20, 2024

First Posted (Actual)

September 23, 2024

Study Record Updates

Last Update Posted (Actual)

April 28, 2026

Last Update Submitted That Met QC Criteria

April 23, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BUHS-IRB # R-063/24

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All data will be shared

IPD Sharing Time Frame

The IPD data will become accessible one year after publication and will remain available indefinitely.

IPD Sharing Access Criteria

All the data will be accessible to everyone.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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