A Pilot Study of the Grapefruit Flavonoid Naringenin for HCV Infection

NCT01091077 | Completed Phase 1 DMC

• 1 other identifier: GFN-001
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatitis C virus when it leaves the cells in the liver is bound to a type of fat. An component of grapefruit could block this fat and thus lower the amount of virus in the blood stream. We propose that treatment with this ingredient, called naringenin, could be used to block this fat and HCV in persons infected with hepatitis C.

Conditions

Hepatitis C Virus; HCV Infection; Chronic HCV; Hepatitis C

Keywords

dietary supplement

Outcome Measures

Primary Outcomes (1)

• Naringenin pharmacokinetic curves

  Level of naringenin will be measured by HPLC at time 0, 30, 40, 90, 120, 150, and 180 min and at 4, 5, 6, 7, 8, and 12 hours.

  12 hours

Secondary Outcomes (5)

• Safety

  12 hours

• Changes in HCV RNA levels

  12 hours

• Homeostatic model assessment-insulin resistance (HOMA-IR)

  24 hours

• Lipid levels: Cholesterol and triglyceride levels

  24 hours

• Liver enzyme levels

  24 hours

Study Arms (1)

Naringenin

PLACEBO COMPARATOR

Single dose of naringenin, compared to placebo in the same individual.

Dietary Supplement: Naringenin

Interventions

Naringenin DIETARY_SUPPLEMENT

1 gram of naringenin mixed with 16 grams of hydroxypropyl-β-cyclodextrin in 250 mL of water

Also known as: Grapefruit

Naringenin

Eligibility Criteria

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

You may qualify if:

• HCV infection as documented by any licensed ELISA test kit any time prior to study entry.
• Documentation of chronic high-titer HCV infection, as defined as a positive HCV viral load \>400,000 IU/ML measured within 2 years prior to study entry and after the last interferon-based treatment course.
• HCV genotype - all genotypes are eligible for this trial
• Prior (but not current) treatment with interferon-based therapies are allowed
• Subjects with documented or suspected hepatic cirrhosis must have a Modified Child-Pugh-Turcotte (CPT) Score of 5 or less within 42 days prior to study entry.

You may not qualify if:

• Presence of known causes of significant liver disease including chronic or acute hepatitis B, acute hepatitis A, autoimmune hepatitis, hemochromatosis, or homozygote alpha-1 antitrypsin deficiency.
• Evidence of decompensated liver disease manifested by presence of or history of ascites, variceal bleeding, or hepatic encephalopathy, and/or a Child-Pugh score of 6 or higher.
• History of major organ transplantation, including liver, with an active, functioning graft
• Candidates for liver transplant, as evidenced by active listing
• Receipt of HCV treatment within 28 days prior to study entry.
• Breast-feeding.
• Pregnancy, or considering getting pregnant within 1 month
• Use of lipid-lowering drugs (i.e. HMG-CoA reductase inhibitors, fibrates, omega-3 fatty acids, bile acid sequestrants, ezetimibe, and niacin derivatives), within 3 months prior to study entry
• Use of drugs with known interactions with grapefruit juice
• Known HIV infection
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• History of an adverse reaction to citrus fruits
• History of uncontrolled seizure disorder.
• Uncontrolled depression or other psychiatric disorder such as untreated Grade 3 psychiatric disorder, Grade 3 disorder not amenable to medical intervention, or any hospitalization within the past 52 weeks that in the opinion of the site investigator might preclude tolerability of study requirements.
• History of autoimmune processes, including but not limited to Crohn's disease, ulcerative colitis, severe psoriasis, rheumatoid arthritis, that have been exacerbated by previous interferon use.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Harvard University: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Nahmias Y, Goldwasser J, Casali M, van Poll D, Wakita T, Chung RT, Yarmush ML. Apolipoprotein B-dependent hepatitis C virus secretion is inhibited by the grapefruit flavonoid naringenin. Hepatology. 2008 May;47(5):1437-45. doi: 10.1002/hep.22197.

  PMID: 18393287 BACKGROUND

MeSH Terms

Conditions

Hepatitis C

Interventions

naringenin; grapefruit seed extract

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Arthur Y Kim, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: March 17, 2010
• First Posted: March 23, 2010
• Study Start: June 1, 2009
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: September 23, 2015

Record last verified: 2015-09

Locations

US (1)