Lactoferrin in Treatment of Fe Deficient Anemia In Cirrhosis

NCT ID: NCT04335058

Last Updated: 2023-05-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-01
• Study Completion Date: 2023-12-31

Brief 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.

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.

Conditions

Iron Deficiency Anemia; Chronic Liver Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Lactoferrin + Iron Supplement

Intervention Type: DRUG

Lactoferrin 100 mg twice daily +oral iron

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

Group Type: ACTIVE_COMPARATOR

Iron Supplement

Intervention Type: DRUG

Oral iron supplement alone

Interventions

Lactoferrin + Iron Supplement

Lactoferrin 100 mg twice daily +oral iron

Intervention Type: DRUG

Iron Supplement

Oral iron supplement alone

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role: lead

Responsible Party

Madhumita Premkumar

Assistant professor, Department of Hepatology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Madhumita Premkumar, DM

Role: PRINCIPAL_INVESTIGATOR

Post Graduate Institute of Medical Education and Research, Chandigarh

Locations

Postgraduate Institute of Medical Education and Research

Chandigarh, , India

Site Status: RECRUITING

Countries

India

Central Contacts

Madhumita Premkumar, DM

Role: CONTACT

drmadhumitap@gmail.com

01722756344

Facility Contacts

Madhumita PREMKUMAR, DM

Role: primary

drmadhumitap@gmail.com

01722756344

References

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.

Reference Type: BACKGROUND

PMID: 11922584 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 19519436 (View on PubMed)

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

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 19809023 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19652425 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30298070 (View on PubMed)

Other Identifiers

IEC/11/2019/1596

Identifier Type: -

Identifier Source: org_study_id