Feasibility Test of Folic Acid on Acute Kidney Injury

NCT07013136 | Not Yet Recruiting Early Phase 1

• 1 other identifier: Folate_AKI-RAINER-2024
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the feasibility of folic acid supplementation as a treatment for adult patients with acute kidney injury (AKI) receiving hospital care. The main question it aims to answer is: Is it feasible to conduct a fully-powered randomized controlled trial (RCT) to assess the efficacy and safety of folic acid supplementation in AKI management? Researchers will compare two groups (usual care vs. usual care + 5 mg folic acid) to determine the feasibility of folic acid supplementation and estimate the sample size required for a fully powered RCT. Participants will:

1. 1.Receive either usual care, or usual care combined with oral folic acid (5 mg daily) until AKI resolution (up to 30 days);
2. 2.Undergo regular monitoring during hospitalization and follow-ups at 3 months and one year post-discharge.

Conditions

Acute Kidney Injury

Keywords

Acute kidney injury; Clinical trial; Feasibility study; Folate; 5-Methyltetrahydrofolate; Repurpose

Outcome Measures

Primary Outcomes (2)

• The feasibility of intervention

  A preset feasibility goal of 70% or greater of recognized patients joining the study with 70% or more adherence to scheduled dosages of the intervention until AKI is resolved or to a maximum of 30 days \[Binary Y/N\].

  From enrollment to the end of treatment up to 30 days

• 30-day Severe Adverse Events

  The incidence of severe adverse events (SAEs) in patients receiving folate supplementation \[Binary Y/N\].

  From enrollment to the end of treatment up to 30 days

Secondary Outcomes (9)

• Screening rate

  At enrollment

• Consent rate

  At enrollment

• Time from presentation to consent

  At enrollment

• Acceptability of a future randomized controlled trial (RCT)

  From enrollment to the end of treatment up to 30 days

• Retrieval rate of patient outcomes

  From enrollment to the end of treatment at 30 days, 3 months and one year

Study Arms (2)

Arm 1. Usual care

NO INTERVENTION

Usual care is given until AKI is resolved.

Arm 2. Folic acid 5 mg + Usual care

EXPERIMENTAL

Oral folic acid 5mg is given once a day until AKI is resolved\*, to a maximum of 30 days\*\*.

Drug: Folic Acid 5 MG

Interventions

Folic Acid 5 MG DRUG

In this study, oral folic acid at 5 mg/d (\~83.3 μg/kg) is chosen. In a rat model of AKI with ischaemia-reperfusion, intraperitoneal injection of 5-methyltetrahydrofolate (5-MTHF) at 3 μg/kg body weight twice (30 min before ischaemia and 3 h after reperfusion) improved kidney function and alleviated oxidative stress within 24 hours. The average body weight is around 60 kg for Chinese. Considering the oral route often requires larger doses than injection to produce the same effect, oral folic acid at 5 mg/d (\~83.3 μg/kg) is chosen to test its effect on AKI. Depending on the clinical condition, the therapeutic dose of folic acid varies. For foetal support during pregnancy, daily doses of 1 mg of folic acid are recommended; for lowering homocysteine, up to 5 mg daily are generally used.

Arm 2. Folic acid 5 mg + Usual care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be eligible for the study if ALL the following are present:
• Adults ≥18 years of age;
• AKI;
• Intended or existing hospitalisation;
• No medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the study;
• Informed consent

You may not qualify if:

• Patients will be excluded from the study if any of the following conditions is present:
• Refusal of consent expressed by the patient, close relative or legally appointed representative;
• Enrolled in other research studies within previous 30 days;
• Not expected to survive 3 days due to renal disease or other co-existing diseases;
• Planned inter-hospital transfer within 3 days;
• Recent surgery (\<30 days);
• Pregnancy;
• Contraindication to folate;
• Already on folate treatment

Sponsors & Collaborators

• The University of Hong Kong: lead
• Queen Mary Hospital, Hong Kong: collaborator

Study Sites (1)

Queen Mary Hospital

Hong Kong, Hong Kong, Hong Kong

Location

Related Publications (14)

• Shelton LM, Park BK, Copple IM. Role of Nrf2 in protection against acute kidney injury. Kidney Int. 2013 Dec;84(6):1090-5. doi: 10.1038/ki.2013.248. Epub 2013 Jun 19.

  PMID: 23783243 BACKGROUND

• Pietrzik K, Bailey L, Shane B. Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2010 Aug;49(8):535-48. doi: 10.2165/11532990-000000000-00000.

  PMID: 20608755 BACKGROUND

• Scaglione F, Panzavolta G. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica. 2014 May;44(5):480-8. doi: 10.3109/00498254.2013.845705. Epub 2014 Feb 4.

  PMID: 24494987 BACKGROUND

• Nikolic T, Petrovic D, Matic S, Turnic TN, Jeremic J, Radonjic K, Srejovic I, Zivkovic V, Bolevich S, Bolevich S, Jakovljevic V. The influence of folic acid-induced acute kidney injury on cardiac function and redox status in rats. Naunyn Schmiedebergs Arch Pharmacol. 2020 Jan;393(1):99-109. doi: 10.1007/s00210-019-01717-z. Epub 2019 Aug 27.

  PMID: 31455992 BACKGROUND

• Matsuura R, Doi K, Rabb H. Acute kidney injury and distant organ dysfunction-network system analysis. Kidney Int. 2023 Jun;103(6):1041-1055. doi: 10.1016/j.kint.2023.03.025. Epub 2023 Apr 6.

  PMID: 37030663 BACKGROUND

• Thomas ME, Blaine C, Dawnay A, Devonald MA, Ftouh S, Laing C, Latchem S, Lewington A, Milford DV, Ostermann M. The definition of acute kidney injury and its use in practice. Kidney Int. 2015 Jan;87(1):62-73. doi: 10.1038/ki.2014.328. Epub 2014 Oct 15.

  PMID: 25317932 BACKGROUND

• Yan LJ. Folic acid-induced animal model of kidney disease. Animal Model Exp Med. 2021 Nov 24;4(4):329-342. doi: 10.1002/ame2.12194. eCollection 2021 Dec.

  PMID: 34977484 BACKGROUND

• Sharfuddin AA, Molitoris BA. Pathophysiology of ischemic acute kidney injury. Nat Rev Nephrol. 2011 Apr;7(4):189-200. doi: 10.1038/nrneph.2011.16. Epub 2011 Mar 1.

  PMID: 21364518 BACKGROUND

• Rahman M, Shad F, Smith MC. Acute kidney injury: a guide to diagnosis and management. Am Fam Physician. 2012 Oct 1;86(7):631-9.

  PMID: 23062091 BACKGROUND

• Szeto CC. Perspectives on acute kidney injury strategy: Hong Kong. Nephrology (Carlton). 2018 Oct;23 Suppl 4:104-106. doi: 10.1111/nep.13450.

  PMID: 30298652 BACKGROUND

• Hoste EAJ, Kellum JA, Selby NM, Zarbock A, Palevsky PM, Bagshaw SM, Goldstein SL, Cerda J, Chawla LS. Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol. 2018 Oct;14(10):607-625. doi: 10.1038/s41581-018-0052-0.

  PMID: 30135570 BACKGROUND

• Dasta JF, Kane-Gill S. Review of the Literature on the Costs Associated With Acute Kidney Injury. J Pharm Pract. 2019 Jun;32(3):292-302. doi: 10.1177/0897190019852556.

  PMID: 31291842 BACKGROUND

• Negi S, Koreeda D, Kobayashi S, Yano T, Tatsuta K, Mima T, Shigematsu T, Ohya M. Acute kidney injury: Epidemiology, outcomes, complications, and therapeutic strategies. Semin Dial. 2018 Sep;31(5):519-527. doi: 10.1111/sdi.12705. Epub 2018 May 8.

  PMID: 29738093 BACKGROUND

• Lameire NH, Bagga A, Cruz D, De Maeseneer J, Endre Z, Kellum JA, Liu KD, Mehta RL, Pannu N, Van Biesen W, Vanholder R. Acute kidney injury: an increasing global concern. Lancet. 2013 Jul 13;382(9887):170-9. doi: 10.1016/S0140-6736(13)60647-9. Epub 2013 May 31.

  PMID: 23727171 BACKGROUND

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Folic Acid

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Timothy H Rainer, MBBCh

  Department of Emergency Medicine, The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Timothy H Rainer, MBBCh

CONTACT

852 + 39176846; thrainer@hku.hk

Yaqing Jiao, PhD

CONTACT

852 + 39179115; yqjiao@hku.hk

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2025
• First Posted: June 10, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: July 15, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)