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Hepatitis C VirusPhase 1NCT01091077

A Pilot Study of the Grapefruit Flavonoid Naringenin for HCV Infection

A Phase 1 study testing Naringenin in people with Hepatitis C Virus and HCV Infection, run by Massachusetts General Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Hepatitis C Virus, HCV Infection, Chronic HCV
What is being tested?
Naringenin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
7 participants
Where
1 siteUnited States
Study dates
Jun 2009to Aug 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.
  • Any systemic antineoplastic or immunomodulatory treatment or radiation within 24 weeks prior to study entry.
  • Serious illness including malignancy, active symptomatic coronary artery disease within 24 weeks prior to study entry, or other chronic medical conditions that may preclude completion of the protocol in the investigator's opinion.
  • Past history of estrogen-responsive breast cancer
  • Use of antidiabetic medications within 12 weeks prior to study entry.
  • Fasting plasma glucose ≥126 mg/dL within 42 days prior to study entry or currently or previously treated at any time for diabetes with measures other than diet. NOTE: Women with a history of gestational diabetes not requiring any treatment for diabetes before or after pregnancy are eligible for participation. Subjects with diabetes/hyperglycemia occurring in the context of short-term use of corticosteroids, growth hormone, or other diabetogenic medication, but not requiring any treatment for diabetes after discontinuation of the implicated medication, are eligible to participate. Subjects with diabetes/hyperglycemia following an episode of pancreatitis who no longer require treatment for diabetes are eligible.
  • Known osteoporosis or receipt of treatment of osteopenia or osteoporosis within 12 weeks prior to study entry with the following medications: risedronate (Actonel®), ibandronate (Boniva®), etidronate (Didronel®), raloxifene (Evista®), teriparatide (Forteo®), aledronate (Fosamax®), calcitonin (Miacalcin®).
  • Inability to tolerate consumption of an ice cream-based milkshake.
  • Regular and excessive use of alcohol defined as self-reported alcohol intake >120 g of alcohol/week in a male or >60 g alcohol/week in a female within 12 weeks immediately prior to study entry.
  • Unwilling to restrict alcohol use during the study to ≤120g alcohol/week in a male or ≤60 g alcohol/week in a female.
  • Unwilling to restrict diet during the study (both Step 1 and Step 2).
  • Known glucocorticoid use in supraphysiologic doses (prednisone >10 mg/day or equivalent doses of other glucocorticoids) within 12 weeks prior to study entry.
  • Known glucocorticoid use in physiologic replacement doses (prednisone ≤10 mg/day or equivalent doses of other glucocorticoids) initiated within 28 days prior to study entry. NOTE: Individuals on physiologic replacement doses of glucocorticoids initiated more than 28 days prior to study entry will not be excluded.
  • History of congestive heart failure corresponding to New York Heart Association Class II or greater
  • Current use of prohibited concomitant medications
  • Current participation in experimental studies that include treatments not approved by the FDA or any blinded treatments.
  • Body mass index (BMI) > 35 kg/m2.
  • Known allergy to food contained within the standard meal (i.e. chicken, soy)
  • Subjects with a history of clinically significant cardiac disease, including a family history of Long QT Syndrome, and/or evidence of the following ECG abnormalities at screening:
  • QTcF (QT corrected using Fridericia's formula, Fridericia's formula: QTcF=QT/(RR^0.333) of > 450 msec; complete or incomplete left or right bundle branch block; intraventricular conduction delay with QRS duration of > 120 msec; bradycardia (< 45 beats per minute);
  • pathologic Q-waves (Q-wave of > 40 msec or depth of > 0.4 to 0.5 V);
  • arrhythmia (an isolated premature ventricular contraction on screening/Day 1 is not exclusionary) ;
  • ventricular pre-excitation;
  • second or third degree heart block.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: A Pilot Study of the Grapefruit Flavonoid Naringenin for the Treatment of HCV Infection

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.

Read the detailed description

The hepatitis C virus is actively secreted by the liver of infected patients while bound to very low density lipoprotein (vLDL). The grapefruit flavonoid naringenin could be used to block vLDL secretion and lower the circulating viral titer.

Hypothesis:

Treatment with naringenin will block vLDL and HCV secretion in persons infected with HCV.

Primary Objective

To study the safety and pharmacokinetics of a single-dose of naringenin

Secondary Objectives

  1. To study the changes in circulating HCV titers during the transition from a fasted to fed state.
  2. To study the changes in circulating HCV titers after administration of the grapefruit flavonoid naringenin.
  3. To study effects of naringenin on vLDL secretion.

This is a single-arm, cross over study where placebo is administered during a transition from a fasted to a fed state, then the protocol is repeated with a single dose of naringenin plus cyclodextrin, using the previous measurements as his/her own control

Being tested
Naringenin
Keywords
dietary supplement
Medical subject headings
Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NaringeninDietary supplement

    Also called Grapefruit

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

Study groups in NCT01091077
Study groupRoleWhat they receive
NaringeninPlacebo comparatorSingle dose of naringenin, compared to placebo in the same individual.
Receives: Dietary Supplement: Naringenin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 hours

Secondary outcomes (5)

  1. Safety

    as indicated by all high-grade signs and symptoms and laboratory values.

    Measured: 12 hours

  2. Changes in HCV RNA levels

    Measured: 12 hours

  3. Homeostatic model assessment-insulin resistance (HOMA-IR)

    Measured: 24 hours

  4. Lipid levels: Cholesterol and triglyceride levels

    Measured: 24 hours

  5. Liver enzyme levels

    ALT and AST at entry and end of steps 1 and 2.

    Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Mar 2010 (estimated)
  2. Study startJun 2009
  3. Primary completionAug 2013
  4. Study completionAug 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01091077
Sponsor's protocol ID
GFN-001
Status last verified
Sep 2015
First submitted
17 Mar 2010
Last updated
23 Sep 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 18393287

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Naringenin in people with Hepatitis C Virus and HCV Infection, run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Naringenin pharmacokinetic curves (time frame: 12 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01091077, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2015.

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