Safety IssuesEarly Phase 1CitrusNCT03582553
Safety and Pharmacokinetics of an Extract of Naringenin
A Early Phase 1 study testing Naringenin in people with Safety Issues and Pharmacokinetics, run by Pennington Biomedical Research Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Safety Issues, Pharmacokinetics
- What is being tested?
- Naringenin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 25 May 2018to 28 Sep 2018
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Pennington Biomedical Research Center
Baton Rouge, Louisiana, 70808
About this study
Official title: Clinical Safety and Pharmacokinetic Evaluation of Naringenin: Single Dose Escalation Randomized Double Blind Controlled Trial
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.
Read the 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.
- Conditions
- Safety Issues, Pharmacokinetics
- Being tested
- Naringenin, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaringeninDietary supplement
An extract of Citrus Sinensis containing naringenin and its precursor naringin
PlaceboOther
Cellulose
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Blood will be drawn over a period of 24 hours following ingestion of the 150 and 600mg doses of naringenin and serum concentrations will be measured. The area under the serum concentration versus time curve will be determined.
Measured: 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
Blood will be drawn over a period of 24 hours following ingestion of the 150 and 600mg doses of naringenin and serum concentrations will be measured. The maximal serum concentration will be determined.
Measured: 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
Blood will be drawn over a period of 24 hours following ingestion of the 150 and 600mg doses of naringenin and serum naringenin concentrations will be measured. The time to peak serum naringenin concentration will be determined.
Measured: 24 hours
Measurement of Half Life of Naringenin at 150 and 600 mg Doses
Blood will be drawn over a period of 24 hours following ingestion of the 150 and 600mg doses of naringenin and serum naringenin concentrations will be measured. The half life of naringenin will be determined.
Measured: 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
Blood will be drawn over a period of 24 hours following ingestion of the 150 and 600mg doses of naringenin and serum naringenin concentrations will be measured. The apparent oral clearance of naringenin will be determined.
Measured: 0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours
Measurement of Four-hour Concentration of Serum Naringenin at 300 and 900 mg Doses
Blood will be drawn at 0 hours and 4 hours following ingestion of the 300 and 900mg doses of naringenin and serum naringenin concentrations will be measured.
Measured: 0 and 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2018
- Study start25 May 2018
- Primary completion28 Sep 2018
- Study completion28 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Safety IssuesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pennington Biomedical Research Center
- Sponsor type
- University, hospital or other
- Collaborators
- Louisiana Clinical and Translational Science Center
- Responsible party
- Principal investigator, Candida Rebello, Pennington Biomedical Research Center
- Investigators
- Candida Rebello, Principal investigator, Pennington Biomedical Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03582553
- Sponsor's protocol ID
- 2018-011
- Acronym
- Citrus
- Status last verified
- Jan 2020
- First submitted
- 22 Jun 2018
- Last updated
- 18 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 27146015
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Safety and Pharmacokinetic Evaluation of Naringenin: Single Dose Escalation Randomized Double Blind Controlled Trial
- ClinicalTrials.gov ID
- NCT03582553
- Acronym / sponsor ID
- Citrus / 2018-011
- Conditions
- Safety Issues, Pharmacokinetics
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Pennington Biomedical Research CenterUniversity, hospital or other
- Collaborators
- Louisiana Clinical and Translational Science Center
- Study start
- 25 May 2018 (actual)
- Primary completion
- 28 Sep 2018 (actual)
- Study completion
- 28 Sep 2018 (actual)
- First posted
- 11 Jul 2018 (actual)
- Results
- Posted 18 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
- 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.
| Arm | Type | Receives |
|---|---|---|
| 150 mg dose | Experimental | Dietary Supplement: NaringeninBlood 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. |
| 300 mg dose | Experimental | Dietary Supplement: NaringeninBlood 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. |
| 600 mg dose | Experimental | Dietary Supplement: NaringeninBlood 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. |
| 900 mg dose | Experimental | Dietary Supplement: NaringeninBlood 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. |
| Placebo | Placebo comparator | Other: PlaceboSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NaringeninAn extract of Citrus Sinensis containing naringenin and its precursor naringin | Dietary supplement | 150 mg dose, 300 mg dose, 600 mg dose, 900 mg dose |
| PlaceboCellulose | Other | Placebo |
Primary outcome
Incidence of Treatment-emergent Adverse Events Following a Single Dose of a Citrus Extract of Naringenin
Time frame: Adverse events were collected over approximately five weeks which included three study days and two washout periods of at least one week.
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.
6 secondary outcomes
Measurement of Area Under the Serum Naringenin Concentration Versus Time Curve at 150 and 600 mg Doses
Time frame: 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
Time frame: 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
Time frame: 24 hours
Measurement of Half Life of Naringenin at 150 and 600 mg Doses
Time frame: 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
Time frame: 0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours
Measurement of Four-hour Concentration of Serum Naringenin at 300 and 900 mg Doses
Time frame: 0 and 4 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27146015Mulvihill 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Candida Rebello principal investigator
Pennington Biomedical Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Naringenin in people with Safety Issues and Pharmacokinetics, run by Pennington Biomedical Research Center 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 4 inclusion and 13 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 18 Jan 2020. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Incidence of Treatment-emergent Adverse Events Following a Single Dose of a Citrus Extract of Naringenin (time frame: Adverse events were collected over approximately five weeks which included three study days and two washout periods of at least one week.). 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 NCT03582553, 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 18 Jan 2020.