Safety and Pharmacokinetics of an Extract of Naringenin

NCT03582553 | Completed Early Phase 1 Results

• 1 other identifier: 2018-011
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the safety of administering single ascending doses (150, 300, 600, and 900 mg) of a citrus extract of the flavonoid narigenin, and assesses the blood concentrations of naringenin following oral administration of the extract.

Conditions

Safety Issues; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-emergent Adverse Events Following a Single Dose of a Citrus Extract of Naringenin

  All adverse events will be recorded following the first administration of the study product or placebo. The study physician in consultation with the coordinator will review and determine whether a subject can be administered the next ascending dose. The cohorts will be run in series. There will be an interval of up to four weeks between the two cohorts. During this time an interim analysis will be conducted and a safety summary of adverse events for Cohort 1 will be compiled and reviewed by the investigators. Dose safety will be investigated by compiling by treatment (e.g. 150 mg dose, 300 mg dose, placebo) a list of adverse events. The frequency of these events will be counted and compared with the placebo group.

  Adverse events were collected over approximately five weeks which included three study days and two washout periods of at least one week.

Secondary Outcomes (6)

• Measurement of Area Under the Serum Naringenin Concentration Versus Time Curve at 150 and 600 mg Doses

  0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours

• Measurement of Maximal Concentration of Serum Naringenin at 150 and 600 mg Doses

  0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours

• Measurement of Time to Peak Concentration of Serum Naringenin at 150 and 600 mg Doses

  24 hours

• Measurement of Half Life of Naringenin at 150 and 600 mg Doses

  0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours

• Measurement of Apparent Oral Clearance of Naringenin at 150 and 600 mg Doses

  0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours

Study Arms (5)

150 mg dose

EXPERIMENTAL

Blood will be drawn at at 0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours to measure serum naringenin concentrations in response to a single 150 mg oral dose of an extract of Citrus sinensis (sweet orange) containing naringenin and its precursor naringin.

Dietary Supplement: Naringenin

300 mg dose

EXPERIMENTAL

Blood will be drawn at at 0, and 4 hours to measure serum naringenin concentrations in response to a single 300 mg oral dose of an extract of Citrus sinensis (sweet orange) containing naringenin and its precursor naringin.

Dietary Supplement: Naringenin

600 mg dose

EXPERIMENTAL

Blood will be drawn at at 0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours to measure serum naringenin concentrations in response to a single 600 mg oral dose of an extract of Citrus sinensis (sweet orange) containing naringenin and its precursor naringin.

Dietary Supplement: Naringenin

900 mg dose

EXPERIMENTAL

Blood will be drawn at at 0, and 4 hours to measure serum naringenin concentrations in response to a single 900 mg oral dose of an extract of Citrus sinensis (sweet orange) containing naringenin and its precursor naringin.

Dietary Supplement: Naringenin

Placebo

PLACEBO COMPARATOR

Subjects in the first cohort will receive 150 mg and 300 mg ascending doses of naringenin and subjects in the second cohort will receive 600 mg and 900 mg ascending doses of naringenin. Each cohort will also have a placebo group.

Other: Placebo

Interventions

Naringenin DIETARY_SUPPLEMENT

An extract of Citrus Sinensis containing naringenin and its precursor naringin

150 mg dose; 300 mg dose; 600 mg dose; 900 mg dose

Placebo OTHER

Cellulose

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (≥18 years)
• Body mass index between 20 and 35 kg/m2
• Must have fasting blood sugar \<126 mg/dL)
• Must be willing to refrain from consuming citrus fruits and tomato in any form, for 36 hours prior to each test day.

You may not qualify if:

• Report citrus allergies.
• Report a history of cardiovascular disease, diabetes, or cancer
• Have evidence of hepatic disease or dysfunction
• Are currently pregnant or breastfeeding
• Are women of childbearing potential who will not use an effective method of birth control
• Chronically use of medications except over the counter medications that have been stopped 72 hours prior to the study visit
• Report clinically significant GI malabsorption syndromes
• Have clinically significant abnormal laboratory markers
• Anticipate surgery during the study period.
• Report history of substance abuse or alcoholism or significant psychiatric disorder that would interfere with the ability to complete the study.
• Have donated blood during the month prior to study entry or plan to do so during the study.
• Have participated in other studies using an investigational drug during the preceding three months.
• Are current smokers or have smoked within the previous three months.

Sponsors & Collaborators

• Pennington Biomedical Research Center: lead
• Louisiana Clinical and Translational Science Center: collaborator

Study Sites (1)

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808, United States

Location

Related Publications (1)

• Mulvihill EE, Burke AC, Huff MW. Citrus Flavonoids as Regulators of Lipoprotein Metabolism and Atherosclerosis. Annu Rev Nutr. 2016 Jul 17;36:275-99. doi: 10.1146/annurev-nutr-071715-050718. Epub 2016 May 4.

  PMID: 27146015 BACKGROUND

MeSH Terms

Interventions

naringenin

Results Point of Contact

• Title: Dr. Candida Rebello
• Organization: Pennington Biomedical Research Center

Candida.Rebello@pbrc.edu

225-763-3159

Study Officials

• Candida Rebello

  Pennington Biomedical Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Except for the pharmacist who will prepare and dispense the capsules, all study staff and the investigators will be blinded to the randomization.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Postdoctoral Researcher

Model Details: The study consists of two cohorts of nine subjects each. In the first cohort subjects will receive the 150 mg dose and proceed to the 300 mg dose only if the 150 mg dose is deemed safe. The study is a double blind randomized controlled crossover trial, therefore, subjects could receive a placebo at the first or second visit. Similarly in the second cohort, 600 mg and 900 mg doses will be evaluated.

Study Record Dates

• First Submitted: June 22, 2018
• First Posted: July 11, 2018
• Study Start: May 25, 2018
• Primary Completion: September 28, 2018
• Study Completion: September 28, 2018
• Last Updated: January 18, 2020
• Results First Posted: January 18, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)