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ThalassemiaNCT04310059

Effect of Folic Acid Supplementation in Pregnant Women Having Thalassaemia Trait

A study testing Folic acid and Materna in people with Thalassemia and Folic Acid Deficiency Anemia, run by The University of Hong Kong.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Folic acid supplementation has been recommended for prevention of neural tube defects in pregnancy when taken periconceptionally up to 12 weeks of gestation. A daily dose of 0.4mg has been endorsed by World Health Organisation to achieve a Red blood cell (RBC) folate level of 906nmol/L (400ng/mL) for reduction of… Read more about this study

Who is it for?
Ages 18 years and older, women onlyHealthy volunteers can take part
Conditions the study is for
Thalassemia, Folic Acid Deficiency Anemia
What is being tested?
Folic acid and Materna
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
270 participants
Where
No sites listed yet
Study dates
1 Jul 2024to 31 Jul 2026
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Singleton pregnancy
  • Alpha thalassaemia trait
  • Beta thalassaemia trait

Who cannot join

  • Women taking over 0.6mg folic acid daily for 3 months or more prior to and during pregnancy
  • Gestational age > 16 weeks at first antenatal visit
  • Women age =< 18 years old
  • Booking BMI =< 18 or >= 35
  • Serum ferritin level < 30ug/L or 68 pmol/L
  • Concomitant alpha and beta thalassaemia
Show all 16Show fewer
  • Hb H disease
  • Beta thalassaemia major
  • Beta thalassaemia intermediate
  • Thalassaemia other than alpha or beta type
  • Women on long term medications
  • Women with risk factors for NTD
  • Women with known epilepsy
  • Women with bariatric surgery or malabsorption diseases
  • Women with known MTHFR polymorphism
  • Vegetarian

Trial locations and contacts

No sites are listed yet.

Pui Wah Hui, MD contact

852-22553402

apwhui@hku.hk

About this study

Official title: A Randomized Controlled Trial to Study the Effect of Folic Acid Supplementation in Pregnant Women Having Thalassaemia Trait

Folic acid supplementation has been recommended for prevention of neural tube defects in pregnancy when taken periconceptionally up to 12 weeks of gestation. A daily dose of 0.4mg has been endorsed by World Health Organisation to achieve a Red blood cell (RBC) folate level of 906nmol/L (400ng/mL) for reduction of neural tube defect. Hong Kong has no policy on food fortification. Research data conducted in countries with food fortification may not be applicable. It is therefore essential to study the baseline folate status in pregnant women locally.

For pregnant women with thalassaemia, they are believed to have a higher risk of folate deficiency because of an increased rate of erythropoiesis and chronic haemolysis. However, information on folate level of thalassaemia trait in pregnancy is scanty. Unmetabolized folic acid has been detected in maternal and fetal blood when daily dosage greater than 0.8-1mg was taken. In term of the dosage and duration of folic acid supplementation after 12 weeks of gestation, the practice varies widely among public hospitals and Maternity \& Child Health Care centres. It is therefore essential to study the optimal dosage of folic acid supplementation in women with thalassaemia.

Read the detailed description

Folic acid supplementation is well established for its role in prevention of neural tube defects (NTD) when taken periconceptionally up to 12 weeks of gestation. The naturally occurring form, folate, is a water soluble B vitamin (B9) that is mostly present in dark green leafy vegetables and legumes. However, it is only 50% bioavailable. Folic acid, on the contrary, as a synthetic form of folate is almost completely bioavailable especially when administered in an empty stomach. It has been endorsed by World Health Organisation that RBC folate cutoff of 906 nmol/L (400ng/mL) is required for reduction of NTD. This level is only achievable by taking Folic acid supplementation of 0.4mg/day. Women at higher risk of having recurrent NTD is recommended to take higher dose at 4mg/day.

Patients with thalassaemia have an increased rate of erythropoiesis and chronic haemolysis. They are believed to have a higher rate of folate turnover and consequentially higher risk of folate deficiency. Guideline from Royal College of Obstetricians and Gynaecologists recommends daily intake of 5mg folic acid preconceptionally to prevent NTD. But, it does not specify whether this dosage is applicable to all types and degrees of thalassaemias and research data on the optimal dosage is lacking.

In addition to prevention of NTD, the supplementation of folic acid is also recommended for pregnant thalassaemia women for prevention of antenatal anaemia. In a retrospective study of Chinese population reported in 1989, women with beta-thalassaemia minor taking additional 5mg folic acid had higher pre-delivery haemoglobin concentration of 10.1 g/dL compared to haemoglobin level of 9.7 g/dL in the group taking Obimin (a pregnancy supplement containing 0.25mg folic acid and 90 mg ferrous fumarate). However, there was no further randomised controlled trial to validate this observation. Though a higher folic acid supplementation was believed to be beneficial in prevention of antenatal anaemia, unmetabolized folic acid were detected in maternal and fetal blood when daily dosage greater than 0.8-1mg was taken. Moreover, a higher rate of urinary excretion of folic acid was also observed in pregnant women receiving higher dosage of folic acid supplementation.

In non-pregnant beta thalassaemia major patients, folic acid supplementation at 1 mg daily was advised as cessation of which could lead to a significant reduction in serum folate. This has been counter-proposed by the observation of normal to high serum folate levels in transfusion dependent thalassaemia receiving optimal transfusion. Indeed, folic acid supplementation should be considered for non-transfusion dependent thalassaemia as excessive erythropoiesis is required to maintain satisfactory haemoglobin.

Folate level drops during pregnancy to puerperal period. Information on folate level of thalassaemia trait in pregnancy is scanty. In a paper published in 1985, no difference in serum folate was found between normal women and women with thalassaemia trait, and hence usual supplementation was suggested.

Hong Kong has no policy on food fortification. Research data conducted in countries with food fortification may not be applicable. The folate status may have been changed in last few decades because of better general nutritional status and public knowledge of preconception folic acid supplementation. The preparation of 5mg folic acid is available in all public hospitals and preparation of 0.5mg folic acid is recently introduced. As such, the 5mg folic acid prescription is traditionally adopted and this can be a result of its availability. However, the practice varies widely among public hospitals and Maternity \& Child Health Care centres. There is no standardised guideline on the dosage and indications of folic acid supplementation for pregnant thalassaemic women. More importantly, no recent data on the baseline folate status in pregnant women with thalassaemia is available locally.

Patient blood management in Obstetrics has been advocated with an aim to minimize blood loss by maintaining haemoglobin levels, reduce blood transfusion and optimize patient outcome. Identification and treatment of maternal anaemia is one of the three main pillars to achieve it. Even though thalassaemia can be considered as a risk factor for NTD, it remains controversial as to how much folic acid supplementation is adequate for pregnant women with thalassaemia trait in prevention of maternal anaemia which is a key element in maternity care.

Being tested
Folic acid, Materna
Medical subject headings
Thalassemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Folic acidDietary supplement

    women will be randomised into one of the three groups. Group A - Folic acid 5mg/day Group B - Folic acid 0.5mg/day Group C - Materna one tablet/day (a pregnancy supplement containing 0.6mg folic acid)

  • MaternaDietary supplement

    Materna

Study groups in NCT04310059
Study groupRoleWhat they receive
Folic acid 5mgActive comparatorNot described
Receives: Dietary Supplement: Folic acid
Folic acid 0.5mgActive comparatorNot described
Receives: Dietary Supplement: Folic acid
MaternaActive comparatorNot described
Receives: Dietary Supplement: Materna

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Haemoglobin level

    Measured: Change in level throughout the pregnancy, up to 42 weeks

  2. Maternal RBC folate concentration

    Measured: Change in level throughout the pregnancy, up to 42 weeks

  3. Maternal serum folate concentration

    Measured: Change in level throughout the pregnancy, up to 42 weeks

  4. Cord blood RBC

    Measured: Upon birth

  5. Cord blood serum folate concentration

    Measured: Upon birth

Secondary outcomes (3)
  1. Ferritin level

    Measured: Change in level throughout the pregnancy, up to 42 weeks

  2. Maternal Vitamin B12

    Measured: Maternal Vitamin B12 at first antenatal visit

  3. Cord blood vitamin B12

    Measured: Cord blood vitamin B12 upon birth

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2020
  2. Study start1 Jul 2024 (estimated)
  3. Primary completion31 Jul 2025 (estimated)
  4. Study completion31 Jul 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
270 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04310059
Sponsor's protocol ID
UW 20-084
Status last verified
Nov 2023
First submitted
5 Mar 2020
Last updated
29 Nov 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Daly LE, Kirke PN, Molloy A, Weir DG, Scott JM. Folate levels and neural tube defects. Implications for prevention. JAMA. 1995 Dec 6;274(21):1698-702. doi: 10.1001/jama.1995.03530210052030.

    PubMed 7474275
  • Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992 Dec 24;327(26):1832-5. doi: 10.1056/NEJM199212243272602.

    PubMed 1307234
  • Crider KS, Devine O, Hao L, Dowling NF, Li S, Molloy AM, Li Z, Zhu J, Berry RJ. Population red blood cell folate concentrations for prevention of neural tube defects: Bayesian model. BMJ. 2014 Jul 29;349:g4554. doi: 10.1136/bmj.g4554.

    PubMed 25073783
  • US Preventive Services Task Force; Bibbins-Domingo K, Grossman DC, Curry SJ, Davidson KW, Epling JW Jr, Garcia FA, Kemper AR, Krist AH, Kurth AE, Landefeld CS, Mangione CM, Phillips WR, Phipps MG, Pignone MP, Silverstein M, Tseng CW. Folic Acid Supplementation for the Prevention of Neural Tube Defects: US Preventive Services Task Force Recommendation Statement. JAMA. 2017 Jan 10;317(2):183-189. doi: 10.1001/jama.2016.19438.

    PubMed 28097362
  • Cordero AM, Crider KS, Rogers LM, Cannon MJ, Berry RJ. Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines. MMWR Morb Mortal Wkly Rep. 2015 Apr 24;64(15):421-3.

    PubMed 25905896
  • Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991 Jul 20;338(8760):131-7.

    PubMed 1677062
  • Management of Beta Thalassaemia in Pregnancy. Green-top Guideline No 66: Royal College of Obstetricians & Gynaecologists; 2014. p. 1-17.

  • Lao TT. Obstetric care for women with thalassemia. Best Pract Res Clin Obstet Gynaecol. 2017 Feb;39:89-100. doi: 10.1016/j.bpobgyn.2016.09.002. Epub 2016 Sep 23.

    PubMed 28341055
  • Leung CF, Lao TT, Chang AM. Effect of folate supplement on pregnant women with beta-thalassaemia minor. Eur J Obstet Gynecol Reprod Biol. 1989 Dec;33(3):209-13. doi: 10.1016/0028-2243(89)90131-7.

    PubMed 2599250
  • Plumptre L, Masih SP, Ly A, Aufreiter S, Sohn KJ, Croxford R, Lausman AY, Berger H, O'Connor DL, Kim YI. High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood. Am J Clin Nutr. 2015 Oct;102(4):848-57. doi: 10.3945/ajcn.115.110783. Epub 2015 Aug 12.

    PubMed 26269367
  • Caudill MA, Cruz AC, Gregory JF 3rd, Hutson AD, Bailey LB. Folate status response to controlled folate intake in pregnant women. J Nutr. 1997 Dec;127(12):2363-70. doi: 10.1093/jn/127.12.2363.

    PubMed 9405587
  • Baghersalimi A, Hemmati Kolachahi H, Darbandi B, Kamran Mavardiani Z, Alizadeh Alinodehi M, Dalili S, Hassanzadeh Rad A. Assessment of Serum Folic Acid and Homocysteine in Thalassemia Major Patients Before and After Folic Acid Supplement Cessation. J Pediatr Hematol Oncol. 2018 Oct;40(7):504-507. doi: 10.1097/MPH.0000000000001295.

    PubMed 30124548
  • Tripathi G, Kalra M, Mahajan A. Folate supplementation in transfusion-dependent thalassemia: Do we really need such high doses? Indian J Med Paediatr Oncol. 2016 Oct-Dec;37(4):305. doi: 10.4103/0971-5851.195746. No abstract available.

    PubMed 28144102
  • Tso SC, Wong RL. Folate status in pregnant Chinese women in Hong Kong. Int J Gynaecol Obstet. 1980;18(4):290-4. doi: 10.1002/j.1879-3479.1980.tb00498.x.

    PubMed 6109674
  • White JM, Richards R, Byrne M, Buchanan T, White YS, Jelenski G. Thalassaemia trait and pregnancy. J Clin Pathol. 1985 Jul;38(7):810-7. doi: 10.1136/jcp.38.7.810.

    PubMed 4019802

Questions about this trial

What is this clinical trial studying?

A study testing Folic acid and Materna in people with Thalassemia and Folic Acid Deficiency Anemia, run by The University of Hong Kong.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 29 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Pui Wah Hui, MD (852-22553402, apwhui@hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Haemoglobin level (time frame: Change in level throughout the pregnancy, up to 42 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04310059, which also lists 19 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2023.

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