Clinical trial NCT03582553: Safety and Pharmacokinetics of an Extract of Naringenin
Official title: Clinical Safety and Pharmacokinetic Evaluation of Naringenin: Single Dose Escalation Randomized Double Blind Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Safety Issues
Pharmacokinetics
Lead sponsor: Pennington Biomedical Research Center
Sponsor class: OTHER
Collaborators: name: Louisiana Clinical and Translational Science Center
First posted: 2018-07-11
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: OTHER

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.

Detailed description: Naringenin is a component of food with therapeutic potential to improve glucose metabolism. In order to explore the mechanisms by which naringenin may increase energy expenditure and improve glucose metabolism in humans, it is of vital importance that the safety, tolerability, and bioavailability of naringenin are evaluated, when administered to humans. This study tests the safety of four doses of a citrus extract of naringenin and measures serum concentrations of naringenin at the 150 mg and 600 mg doses over a period of 24 hours, and at the 300 and 900 mg doses at four hours after subjects have been given the respective doses of naringenin.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Incidence of Treatment-emergent Adverse Events Following a Single Dose of a Citrus Extract of Naringenin
timeFrame: Adverse events were collected over approximately five weeks which included three study days and two washout periods of at least one week.
Secondary outcomes:
measure: Measurement of Area Under the Serum Naringenin Concentration Versus Time Curve at 150 and 600 mg Doses
timeFrame: 0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours
measure: Measurement of Maximal Concentration of Serum Naringenin at 150 and 600 mg Doses
timeFrame: 0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours
measure: Measurement of Time to Peak Concentration of Serum Naringenin at 150 and 600 mg Doses
timeFrame: 24 hours
measure: Measurement of Half Life of Naringenin at 150 and 600 mg Doses
timeFrame: 0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours
measure: Measurement of Apparent Oral Clearance of Naringenin at 150 and 600 mg Doses
timeFrame: 0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours
measure: Measurement of Four-hour Concentration of Serum Naringenin at 300 and 900 mg Doses
timeFrame: 0 and 4 hours
Other outcomes:
Locations:
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
Study officials:
affiliation: Pennington Biomedical Research Center
name: Candida Rebello
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.