Lactoferrin in Treatment of Fe Deficient Anemia In Cirrhosis

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

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.

Study Overview

• Status: Recruiting
• Conditions: Iron Deficiency Anemia; Chronic Liver Failure
• Intervention / Treatment: Drug: Lactoferrin + Iron Supplement; Drug: Iron Supplement

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Chandigarh, India, 160012
    • Recruiting
    • Postgraduate Institute of Medical Education and Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Lactoferrin plus oral iron; Treated for 2 months regularly with oral administration of 100 mg Lactoferrin tablet twice a day before meals with oral administration of 100 mg of elemental iron capsules, one capsule twice daily on an empty stomach, at least 1 hour before or 2 hours after meals	Drug: Lactoferrin + Iron Supplement; Lactoferrin 100 mg twice daily +oral iron
Active Comparator: Oral iron alone; Oral administration of 100 mg of elemental iron capsules, one capsule twice daily on an empty stomach, at least 1 hour before or 2 hours after meals	Drug: Iron Supplement; Oral iron supplement alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Correction of Anemia	Number of participants achieving Hemoglobin level > 12 g/dl	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in Inflammatory markers	IL-1, Hepcidin, Transferrin saturation measured	3 months

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research
• Investigators: Principal Investigator: Madhumita Premkumar, DM, Postgraduate Institute of Medical Education and Research

Publications and helpful links

General Publications

• 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.
• Actor JK, Hwang SA, Kruzel ML. Lactoferrin as a natural immune modulator. Curr Pharm Des. 2009;15(17):1956-73. doi: 10.2174/138161209788453202.
• Elif M, Cooper JA. Upregulation Of Hepcidin Expression By Lactoferrin Administration To Pre-Weanling Mice. Blood, (2013) 122(21), 964.Accessed August 22, 2019.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: April 2, 2020
• First Posted (Actual): April 6, 2020

Study Record Updates

• Last Update Posted (Actual): May 1, 2023
• Last Update Submitted That Met QC Criteria: April 28, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Metabolic Diseases; Hematologic Diseases; Liver Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; End Stage Liver Disease; Liver Failure; Anemia, Iron-Deficiency; Anemia; Physiological Effects of Drugs; Anti-Infective Agents; Trace Elements; Micronutrients; Iron; Lactoferrin
• Other Study ID Numbers: IEC/11/2019/1596

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No