Lactoferrin in Treatment of Fe Deficient Anemia In Cirrhosis

Iron Deficiency Anemia Clinical Trial

Official title:

Lactoferrin With Iron Versus Iron Alone in Treatment of Anemia In Chronic Liver Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04335058
• Other study ID #: IEC/11/2019/1596
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2020
• Est. completion date: December 2023

Study information

• Verified date: April 2023
• Source: Postgraduate Institute of Medical Education and Research
• Contact: Madhumita Premkumar, DM
• Phone: 01722756344
• Email: drmadhumitap[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Iron deficiency and altered homeostasis due to inflammation and decreased iron utilization are main factors involved in anemia in liver disease. Lactoferrin is a first line defence protein for protection against microbial infections and subsequent development of systemic disease as seen with systemic inflammatory response syndrome (SIRS) and sepsis. Lactoferrin with iron has been shown to be efficacious with anemia in chronic disease, in pregnancy and in cancer patients with fewer side effects than oral iron alone. High exposure to iron is associated with increased inflammation which is associated with worse cardiovascular outcomes. Lactoferrin can help reduce the total iron dose and hepatic inflammation.

Description:

Lactoferrin is a highly conserved, monomeric 80 kDa single polypeptide chain contained in most mammalian exocrine secretions, such as milk, saliva and tears, bronchial, and intestinal secretions. LTF is also found in the secondary granules of neutrophils a glycoprotein present in milk, has been demonstrated to possess a multitude of biological functions. Lactoferrin in Inflammation and Sepsis The antimicrobial activity of LTF is well documented and consists of two mechanisms: one is iron dependent and deals with high affinity of LTF to iron (bacteriostatic), and the other one is due to LTF affinity to lipopolysaccharide (LPS) to function as a direct bactericidal agent for Gram-negative organisms. Small changes, such as single nucleotide polymorphisms, can affect outcomes against pathogenic agents . LTF interacts with cell surface receptors involved in "danger signal" recognition [e.g., toll-like receptor (TLR)4, CD14, and CD22]. At the molecular level, LTF seems to reduce LPS-induced monocyte activation and subsequent production of pro-inflammatory mediators. Lactoferrin in Anemia in Liver Disease The hepatic expression of the hepcidin gene is regulated by signals which reflect body iron status and erythropoietic activity. The regulation of hepcidin by iron status includes a signal from the circulating transferrin via hepatocellular transferrin receptor (TfR2). Like transferrin, lactoferrin will deliver iron to hepatocytes but unlike transferrin, lactoferrin cannot deliver iron to erythroid cells. Lactoferrin does not interact with TfR1 or TfR2.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: December 2023
• Est. primary completion date: October 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age 18-75 years

2. Either gender

3. Patients with chronic liver disease with iron deficiency anemia with transferrin saturation<20% and Hemoglobin in Non-pregnant women (15 years of age and above) <12g/dl and in men <13g/dl -

Exclusion Criteria:

1. Those who do not consent to participate in the study

2. Inability to obtain informed consent from patient or relatives

3. Severe preexisting cardiopulmonary disease

4. Renal dysfunction (S. Creatinine = 2mg/dL)

5. Pregnancy/Lactation

6. Post liver transplant patients

7. HIV infection

8. Patients who are on psychoactive drugs, like sedatives or antidepressants

9. Patients who are too sick to carry out the protocol

Related Conditions & MeSH terms

• Anemia
• Anemia, Iron-Deficiency
• Chronic Liver Failure
• End Stage Liver Disease
• Iron Deficiency Anemia
• Liver Failure

Intervention

Drug:
• Lactoferrin + Iron Supplement
Lactoferrin 100 mg twice daily +oral iron
• Iron Supplement
Oral iron supplement alone

Locations

Country	Name	City	State
India	Postgraduate Institute of Medical Education and Research	Chandigarh

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

References & Publications (6)

Actor JK, Hwang SA, Kruzel ML. Lactoferrin as a natural immune modulator. Curr Pharm Des. 2009;15(17):1956-73. doi: 10.2174/138161209788453202. — View Citation

Elif M, Cooper JA. Upregulation Of Hepcidin Expression By Lactoferrin Administration To Pre-Weanling Mice. Blood, (2013) 122(21), 964.Accessed August 22, 2019.

Hayakawa T, Jin CX, Ko SB, Kitagawa M, Ishiguro H. Lactoferrin in gastrointestinal disease. Intern Med. 2009;48(15):1251-4. doi: 10.2169/internalmedicine.48.2199. Epub 2009 Aug 3. — View Citation

Iwasa M, Kaito M, Ikoma J, Takeo M, Imoto I, Adachi Y, Yamauchi K, Koizumi R, Teraguchi S. Lactoferrin inhibits hepatitis C virus viremia in chronic hepatitis C patients with high viral loads and HCV genotype 1b. Am J Gastroenterol. 2002 Mar;97(3):766-7. doi: 10.1111/j.1572-0241.2002.05573.x. No abstract available. — View Citation

Lepanto MS, Rosa L, Cutone A, Conte MP, Paesano R, Valenti P. Efficacy of Lactoferrin Oral Administration in the Treatment of Anemia and Anemia of Inflammation in Pregnant and Non-pregnant Women: An Interventional Study. Front Immunol. 2018 Sep 21;9:2123. doi: 10.3389/fimmu.2018.02123. eCollection 2018. — View Citation

Manzoni P, Rinaldi M, Cattani S, Pugni L, Romeo MG, Messner H, Stolfi I, Decembrino L, Laforgia N, Vagnarelli F, Memo L, Bordignon L, Saia OS, Maule M, Gallo E, Mostert M, Magnani C, Quercia M, Bollani L, Pedicino R, Renzullo L, Betta P, Mosca F, Ferrari F, Magaldi R, Stronati M, Farina D; Italian Task Force for the Study and Prevention of Neonatal Fungal Infections, Italian Society of Neonatology. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA. 2009 Oct 7;302(13):1421-8. doi: 10.1001/jama.2009.1403. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correction of Anemia	Number of participants achieving Hemoglobin level > 12 g/dl iron deficiency anemia in patients with Chronic Liver Disease of any etiology.	1 months
Primary	Correction of Anemia	Number of participants achieving Hemoglobin level > 12 g/dl	3 months
Secondary	Reduction in Inflammatory markers	IL-1, Hepcidin, Transferrin saturation measured	3 months