Effect of omeprazole or resveratrol on iron status in thalassemia

ISRCTN	ISRCTN73258526
DOI	https://doi.org/10.1186/ISRCTN73258526
Secondary identifying numbers	National Research Council of Thailand Grant number: N42A670732

Submission date: 03/01/2025
Registration date: 08/01/2025
Last edited: 06/01/2025

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Haematological Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Thalassemia is a common hereditary disorder affecting about 1% of the population in Thailand. It results from the defective production of globin chains, leading to symptoms like anemia, jaundice, and growth issues. There are two types: transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). TDT patients often develop iron overload from regular blood transfusions, while NTDT patients absorb too much iron from their diet. This iron overload can cause various health problems. Current treatments include iron chelation therapy, but they have limitations. This study will investigate if using omeprazole (a proton pump inhibitor) and resveratrol (an antioxidant) can help reduce iron absorption and improve treatment for NTDT patients.

Who can participate?
NTDT patients at Maharaj Nakorn Chiang Mai Hospital in Thailand

What does the study involve?
Participants will be divided into three groups of 20, each receiving either a placebo (20 mg maltodextrin), 20 mg omeprazole, or 250 mg resveratrol, taken twice daily before meals for 6 months. All groups will continue with standard treatments like iron chelators, folic acid, vitamin D, calcium supplements, and lifestyle changes. Patients will have appointments at the start, 3 months, and 6 months to monitor clinical signs and blood parameters. Blood tests will measure various health indicators. The study compounds will be prepared in identical gelatin capsules and distributed in labeled bottles. Group 1 will take omeprazole, Group 2 will take resveratrol, and Group 3 will take a placebo, all twice daily for 6 months.

What are the possible benefits and risks of participating?
Possible benefits: Patients may not benefit from this study because the study drugs may not further decrease serum ferritin. However, the information from this study will be helpful for the treatment of thalassemia patients with iron overload in the future.

Risks of participants:
- Risk from blood drawing that may be pain, bruising, or a less common side-effect which is vasovagal syncope.
- Risk from study drugs: omeprazole may cause you to feel nausea, vomiting, diarrhea, abdominal pain, bloating, constipation, back pain or fewer side effects which are chest pain, myocardial infarction, intraabdominal infection, lower respiratory tract infection, pancreatitis, osteoporosis or other unexpected side effects.
- Risk from resveratrol is nausea, vomiting, diarrhea or fewer common side-effect is pancreatitis or other unexpected side effects.

Where is the study run from?
Adult thalassemia clinic, Maharaj Nakorn Chiang Mai Hospital, Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

When is the study starting and how long is it expected to run for?
July 2024 to May 2026

Who is funding the study?
1. National Research Council of Thailand
2. Faculty of Medicine Fund, Chiang Mai University, Chiang Mai Thailand (under processing)

Who is the main contact?
Dr. Thanapong Chopetgool, M.D., Resident Hematologist, chopetgoolden@gmail.com

Contact information

Dr Thanapong Chopetgool
Public, Scientific, Principal Investigator

Division of Hematology, Department of Internal Medicine, Chiang Mai University
Chiang Mai
50200
Thailand

Phone	+66 930748844
Email	chopetgoolden@gmail.com

Study information

Study design	Single-center interventional randomized placebo-controlled clinical trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	University/medical school/dental school
Study type	Efficacy
Participant information sheet	46637_PIS.pdf
Scientific title	Adjunct omeprazole or resveratrol in non-transfusion dependent thalassemia patients with secondary hemochromatosis: a randomized, double-blind, placebo-controlled trial
Study objectives	Adjunctive omeprazole or resveratrol in combination with iron chelators could reduce serum ferritin compared with placebo in thalassemia patients with iron overload. The primary study objective: To evaluate the efficacy of adjunct omeprazole or resveratrol in combination with iron chelators in reducing serum ferritin compared to placebo in non-transfusion-dependent thalassemia patients. Secondary objectives are: 1. Evaluate the efficacy of adjunct omeprazole or resveratrol in combination with iron chelators in reducing labile plasma iron (LPI), non-transferrin bound iron (NTBI) and serum iron (SI) compared to placebo 2. Study the association between adjunct omeprazole or resveratrol in combination with iron chelators and the levels of ERFE and hepcidin (Hcd) 3. Study the association between resveratrol and changes in HbF levels 4. Assess the adverse effects of adjunct omeprazole or resveratrol with iron chelators
Ethics approval(s)	Approved 17/12/2024, Office of Research Ethics (Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; +66 53936643; researchmed@cmu.ac.th), ref: 476/2024
Health condition(s) or problem(s) studied	A decrease in serum iron levels in non-transfusion-dependent thalassemia patients
Intervention	The study will be conducted in non-transfusion-dependent thalassemia patients at the Out-patient department numbers 9 or 23 in Maharaj Nakorn Chiang Mai Hospital, Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. Using the stratified random sampling technique, sixty-three transfusion-dependent thalassemia (TDT) subjects were enrolled in the study, but three dropped out. The sample size was calculated using GPower software version 3.1.9.7, allowing for comparison between the three groups. A repeated measures analysis of variance (ANOVA) F test was employed, incorporating within-between interaction mode. The anticipated effect size for the new compound is 0.50, which is considered large. The statistical power is set at 95% with a significance level (α) of 0.05. Measurements were taken at three points: baseline (month 0), during the first intervention (month 3), and at the end of intervention (month 6). Consequently, the total sample size determined by GPower is 60, with 20 participants allocated to each group. The three groups involve taking 20 mg maltodextrin (placebo), 20 mg omeprazole capsule, and 250 mg resveratrol capsule orally twice daily before meals for 6 months. All groups will receive standard treatments including iron chelators, folic acid supplementation, vitamin D supplementation, calcium supplementation, and lifestyle modifications throughout the study. The patients will be appointed at the first visit, 3 months, and 6 months to evaluate clinical signs and blood parameters levels. Blood samples will be analyzed for complete blood count, hemoglobin types, serum levels of blood urea nitrogen (BUN), creatinine (Cr), electrolytes (e.g., Na+, K+, Ca2+, Mg2+ and phosphates), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), soluble ferritin (sFt), iron (SI), total iron-binding capacity (TIBC), non-transferrin bound iron (NTBI), labile plasma iron (LPI), hepcidin (Hcd), and erythroferrone (ERFE). The three study compounds, including omeprazole, resveratrol, and placebo, will be prepared and filled in gelatin capsules with the same appearance: 20 mg omeprazole capsule, 250 mg resveratrol capsule, and 20 mg maltodextrin. The capsules will be packed in a white plastic bottle (30 capsules each) and labeled with codes under the bottles. The patients in Group 1 will take an omeprazole capsule orally twice daily (total 40 mg/day) in the morning and evening before meals for 6 months. The patients in Group 2 will take a resveratrol capsule orally twice daily (total 500 mg/day) in the morning and evening before meals for 6 months. The patients in Group 3 will take a placebo capsule orally twice daily in the morning and evening before meals for 6 months. Before the commencement of the trial, the results of genotyping and physical assessments were recorded. They documented participants’ age, height, body weight (BW), body mass index (BMI), and the palpability of the liver and spleen. For 60 days, all participants consumed the product daily and were advised to avoid meals rich in polyphenolic components. Blood samples were taken on days 0, 30, and 60 after a 72-hour pause from their iron chelation therapy and just before their subsequent blood transfusion.
Intervention type	Supplement
Primary outcome measure	Changes in serum ferritin measured using an automated Biochemical Analyzer (immuno-chemiluminescence) at baseline, 3 and 6 months
Secondary outcome measures	The following secondary outcome measures are assessed at baseline, 3 and 6 months unless stated: 1. A CBC measured using an automated cell counter 2. Hemoglobin typing measured using cationic-exchange HPLC/DAD at baseline and 6 months. 3. Blood urea nitrogen measured using an automated biochemical analyzer 4. Creatinine measured using an automated biochemical analyzer 5. Electrolytes measured using an automated biochemical analyzer (ion selective method) 6. Aspartate aminotransferase measured using an automated biochemical analyzer (colorimetry) 7. Alanine aminotransferase measured using an automated biochemical analyzer (colorimetry) 8. Alkaline phosphatase measured using an automated biochemical analyzer (colorimetry) 9. Serum iron measured using an automated biochemical analyzer (ferrozine colorimetry) 10. Total iron-binding capacity measured using an automated biochemical analyzer (ferrozine colorimetry) 11. Labile plasma iron measured using Rhodamine B fluorochrome/spectrofluorometry 12. Non-transferrin bound iron measured using NTA/fluorescence chelator beads/flow cytometry a 13. Hepcidin measured using a sandwich enzyme-linked immunoassay 14. Erythroferrone measured using a sandwich enzyme-linked immunoassay 15. Vitamin B12 measured using reversed-phase HPLC/DAD 16. Vitamin D3 measured using a competitive enzyme-linked immunoassay
Overall study start date	01/07/2024
Completion date	05/05/2026

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	20 Years
Upper age limit	65 Years
Sex	Both
Target number of participants	60
Key inclusion criteria	1. Aged 20-65 years old 2. Non-transfusion dependent thalassemia [alpha or beta] diagnosis by HPLC, PCR or gene mutation 3. Hemochromatosis with serum ferritin 300-1000 ng/mL or > 1000 ng/mL with a maximum iron chelator (DFP at 75 mg/kg/day or DFX at 20 mg/kg/day) 4. Concurrent iron chelators without changing dose during 3 months before enrollment and no tendency to adjust the dose of iron chelators between study 5. Inform consent
Key exclusion criteria	Not meeting the participant inclusion criteria
Date of first enrolment	10/02/2025
Date of final enrolment	30/04/2026

Locations

Countries of recruitment

Thailand

Study participating centre

Out-patient department numbers 9 or 23 (Adult thalassemia clinic)

11th Floor, Sriphat Building, Maharaj Nakorn Chiang Mai Hospital, Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University
Chiang Mai
50200
Thailand

Sponsor information

National Research Council of Thailand
Research council

196 Paholyotin Road., Chatuchak
Bangkok
10900
Thailand

Phone	+66 2561 2445
Email	saraban@nrct.go.th
Website	https://dric.nrct.go.th/Index
"ROR"	https://ror.org/018wfhg78

Chiang Mai University
University/education

Faculty of Medicine, 110 Intawaroros Street, Sriphum, Amphur Muang
Chiang Mai
50200
Thailand

Phone	+66 53936209
Email	Researchmed@cmu.ac.th
Website	https://w1.med.cmu.ac.th/research/
"ROR"	https://ror.org/05m2fqn25

Funders

Funder type

Research council

National Research Council of Thailand
Government organisation / National government

Alternative name(s): NRCT
Location: Thailand

Results and Publications

Intention to publish date	01/07/2026
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Planned publication in a peer-reviewed journal such as British Journal of Haematology or American Journal of Hematology
IPD sharing plan	The datasets generated during and/or analyzed during the current study will be available after the study finishes upon request from Dr. Thanapong Chopetgool, MD. from the Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. Telephone numbers (Office) +66 53935482 and (Mobile): +66 930748844. Email: chopetgoolden@gmail.com

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet			03/01/2025	No	Yes
Protocol file			03/01/2025	No	No

Additional files

46637_PIS.pdf
46637_Protocol.pdf

Editorial Notes

03/01/2025: Study's existence confirmed by the Office of Research Ethics, Faculty of Medicine, Chiang Mai University.