Healthy VolunteersGENENCT00953667

The Genetics of Evoked Responses to Niacin and Endotoxemia: The GENE Study

A study testing Immediate Release Niacin, Extended Release Niacin, Endotoxin in people with Healthy Volunteers, run by University of Pennsylvania 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

The purpose of this study is to determine genetic factors that affect responses to niacin therapy and endotoxemia in healthy volunteers. Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers
What is being tested?: Immediate Release Niacin, Extended Release Niacin, Endotoxin
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 400 participants
Where: 1 siteUnited States
Study dates: Jun 2007to Feb 2011
Phase: Interventional
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 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Men and non-pregnant/lactating women between the ages of 18 and 45.
Self reported African American or Caucasian racial-ethnic background.
Body Mass Index (BMI) of ≥ 18 and ≤ 30.
Participants who are able to give written informed consent and willing to comply with all study-related procedures.

Who cannot join

Known clinically manifest atherosclerotic cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease.
History of diabetes mellitus.
Fasting glucose > 126 mg/dL.
History of a non-skin malignancy within the previous 5 years.
Renal insufficiency as defined by creatinine > 1.5 mg/dl at Screening Visit.
History of liver disease or abnormal liver function tests (LFTs) (AST, ALT, Alk. Phos., GGT > 1.5x upper limit of normal (ULN); bilirubin > 2x ULN) at Screening Visit.

Show all 24Show fewer

Men who are unwilling to limit alcohol consumption to <14 alcoholic drinks per week or < 4 alcoholic drinks per occasion (AMA / NIAAA criteria for "at risk" usage levels) while participating in the study.
Women who are unwilling to limit alcohol consumption to < 7 alcoholic drinks per week or < 3 alcoholic drinks per occasion (AMA / NIAAA criteria for "at risk" usage levels) while participating in the study.
Total white blood cell count less than or equal to 3.0 THO/uL.
Hemoglobin below 11.0 g/dL.
Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition or minor active infection.
History of HIV positive.
First degree family history of premature cardiovascular disease event (father or brother if diagnosed at before 55 years of age; mother or sister if diagnosed before 65 years of age).
Patients who have undergone any organ transplant.
Individuals who currently use tobacco products or have done so in the previous 30 days.
Treatment with aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, steroids or any immunomodulatory therapy 2 weeks prior to the Screening Visit.
Treatment with statins, fibrates or niacin 4 weeks prior to the Screening Visit.
Current daily use of Vitamin C > 1000 mg, Beta carotene > 1000 IU, vitamin A > 5000 IU, vitamin E > 400 IU, and selenium > 200 mcg.
Positive urine pregnancy at the Screening Visit.
Participation in another clinical trial within the previous 6 weeks prior to the Screening Visit.
Poorly controlled blood pressure (BP > 160/110) or on any anti-hypertensive medications.
A diagnosis of metabolic syndrome using updated 2004 NCEP ATPIII criteria.
A history of severe lactose intolerance (e.g., intolerance of any milk intake).
Any medical condition or abnormal laboratory value that is judged clinically significant by an investigator.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Pennsylvania
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

The purpose of this study is to determine genetic factors that affect responses to niacin therapy and endotoxemia in healthy volunteers.

Read the detailed description

Niacin is a vitamin that has beneficial effects on cholesterol (a type of fat in the blood) when used in high doses. Different people respond differently to cholesterol lowering doses of niacin, some people have a side effect termed flushing (similar to a hot flash) while others do not and some people have more pronounced effects on cholesterol. Endotoxin or lipopolysaccharide (LPS) is a small part of bacteria (that is no longer living) that can cause many of the effects similar to bacterial infections in humans. However, it can be administered in very small amounts to produce a mild inflammatory response much the same as a 'flu-like" illness. Within 1 ½ -3 hours after giving LPS by vein, a response consisting of fever, chills, headache, nausea and vomiting and generalized aches and pains will occur which lasts up to 6-8 hours. In addition to the flu like symptoms, the inflammation causes changes in cholesterol, triglycerides and glucose clearance. Different people respond differently to endotoxin and inflammation. We are performing this study to see if there are genetic factors that predict how people will respond to niacin and to endotoxin and its inflammatory response.

Conditions: Healthy Volunteers
Being tested: Immediate Release Niacin, Extended Release Niacin, Endotoxin

What participants receive

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

Immediate Release Niacin, Extended Release Niacin, EndotoxinDrug
Also called Niacor, Niaspan
Subjects receive a one-time 1000mg dose of immediate release Niacin (Niacor pills), a one-time 1000mg dose of extended release Niacin (Niaspan pill) and one-time 1ng/kg injection of endotoxin (LPS).

Study groups in NCT00953667
Study group	Role	What they receive
Niacin and Endotoxin	Experimental	All subjects are expected to have the same interventions- Niacin and Endotoxin. Receives: Drug: Immediate Release Niacin, Extended Release Niacin, Endotoxin

What is being measured

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

Baseline and Peak TNF-alpha Values as Categorized by Race and Gender
Measured: Baseline (-15 min, -5 min), and 1, 2, 4, 6, 12, 18, and 24 hours post LPS

Secondary outcomes (1)

Baseline and Peak C-Reactive Protein (CRP) Values as Categorized by Race and Gender
Measured: Baseline ( -15 min, -5 min), and 1, 2, 4, 6, 12, 18, and 24 hours post LPS

Timeline

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

Jun 2007Feb 2011

First posted6 Aug 2009 (estimated)
Study startJun 2007
Primary completionFeb 2011
Study completionFeb 2011

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 (5)Papers the sponsor has linked to this study.
Other trials for Healthy VolunteersStudies of the same condition, open and under way.
More trials run by University of PennsylvaniaThe sponsor's other registered studies.
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: Phase N/A
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 400 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00953667
Sponsor's protocol ID: 805670
Acronym: GENE
Status last verified: Jan 2016
First submitted: 4 Aug 2009
Last updated: 24 Mar 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Ferguson JF, Xue C, Gao Y, Tian T, Shi J, Zhang X, Wang Y, Li YD, Wei Z, Li M, Zhang H, Reilly MP. Tissue-Specific Differential Expression of Novel Genes and Long Intergenic Noncoding RNAs in Humans With Extreme Response to Evoked Endotoxemia. Circ Genom Precis Med. 2018 Nov;11(11):e001907. doi: 10.1161/CIRCGEN.117.001907.
PubMed 30571184
Ferguson JF, Shah RY, Shah R, Mehta NN, Rickels MR, Reilly MP. Activation of innate immunity modulates insulin sensitivity, glucose effectiveness and pancreatic beta-cell function in both African ancestry and European ancestry healthy humans. Metabolism. 2015 Apr;64(4):513-520. doi: 10.1016/j.metabol.2014.12.007. Epub 2014 Dec 26.
PubMed 25579865
Ferguson JF, Ryan MF, Gibney ER, Brennan L, Roche HM, Reilly MP. Dietary isoflavone intake is associated with evoked responses to inflammatory cardiometabolic stimuli and improved glucose homeostasis in healthy volunteers. Nutr Metab Cardiovasc Dis. 2014 Sep;24(9):996-1003. doi: 10.1016/j.numecd.2014.03.010. Epub 2014 Apr 18.
PubMed 24875672
Liu Y, Ferguson JF, Xue C, Ballantyne RL, Silverman IM, Gosai SJ, Serfecz J, Morley MP, Gregory BD, Li M, Reilly MP. Tissue-specific RNA-Seq in human evoked inflammation identifies blood and adipose LincRNA signatures of cardiometabolic diseases. Arterioscler Thromb Vasc Biol. 2014 Apr;34(4):902-12. doi: 10.1161/ATVBAHA.113.303123. Epub 2014 Feb 6.
PubMed 24504737
Ferguson JF, Patel PN, Shah RY, Mulvey CK, Gadi R, Nijjar PS, Usman HM, Mehta NN, Shah R, Master SR, Propert KJ, Reilly MP. Race and gender variation in response to evoked inflammation. J Transl Med. 2013 Mar 12;11:63. doi: 10.1186/1479-5876-11-63.
PubMed 23497455

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 24 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Genetics of Evoked Responses to Niacin and Endotoxemia: The GENE Study
ClinicalTrials.gov ID: NCT00953667
Acronym / sponsor ID: GENE / 805670
Conditions: Healthy Volunteers
Study type: Interventional
Recruitment status: Completed
Enrolment: 400 participants (actual)
Lead sponsor: University of PennsylvaniaUniversity, hospital or other
Study start: Jun 2007
Primary completion: Feb 2011 (actual)
Study completion: Feb 2011 (actual)
First posted: 6 Aug 2009 (estimated)
Results: Posted 24 Mar 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to determine genetic factors that affect responses to niacin therapy and endotoxemia in healthy volunteers.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Niacin and Endotoxin	Experimental	Drug: Immediate Release Niacin, Extended Release Niacin, EndotoxinAll subjects are expected to have the same interventions- Niacin and Endotoxin.

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

Men and non-pregnant/lactating women between the ages of 18 and 45.
Self reported African American or Caucasian racial-ethnic background.
Body Mass Index (BMI) of ≥ 18 and ≤ 30.
Participants who are able to give written informed consent and willing to comply with all study-related procedures.

Key exclusion criteria (24 listed)

Known clinically manifest atherosclerotic cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease.
History of diabetes mellitus.
Fasting glucose > 126 mg/dL.
History of a non-skin malignancy within the previous 5 years.
Renal insufficiency as defined by creatinine > 1.5 mg/dl at Screening Visit.

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
Immediate Release Niacin, Extended Release Niacin, EndotoxinAlso: Niacor, NiaspanSubjects receive a one-time 1000mg dose of immediate release Niacin (Niacor pills), a one-time 1000mg dose of extended release Niacin (Niaspan pill) and one-time 1ng/kg injection of endotoxin (LPS).	Drug	Niacin and Endotoxin

Primary outcome

Baseline and Peak TNF-alpha Values as Categorized by Race and Gender
Time frame: Baseline (-15 min, -5 min), and 1, 2, 4, 6, 12, 18, and 24 hours post LPS

1 secondary outcome

Baseline and Peak C-Reactive Protein (CRP) Values as Categorized by Race and Gender
Time frame: Baseline ( -15 min, -5 min), and 1, 2, 4, 6, 12, 18, and 24 hours post LPS

Results and safety

Results posted to the registry on 24 Mar 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Niacin and Endotoxin	400	277

Primary outcome: Baseline and Peak TNF-alpha Values as Categorized by Race and Gender

Time frame: Baseline (-15 min, -5 min), and 1, 2, 4, 6, 12, 18, and 24 hours post LPS. Median (Inter-Quartile Range). Unit: pg/ml

Measure	Niacin/Endotoxin n = 294
Baseline TNF-alpha in EA males (n=102)	1.08 (0.9 to 1.51)
Peak TNF-alpha in EA males (n=102)	43.48 (23.38 to 67.08)
Baseline TNF-alpha in AA males (n=41)	1.03 (0.73 to 1.37)
Peak TNF-alpha in AA males (n=41)	37.28 (17.78 to 51.64)
Baseline TNF-alpha in EA females (n=91)	1.06 (0.82 to 1.45)
Peak TNF-alpha in EA females (n=91)	43.23 (17.32 to 83.2)
Baseline TNF-alpha in AA females (n=60)	1.13 (0.8 to 1.71)
Peak TNF-alpha in AA females (n=60)	34.01 (19.1 to 58.06)

Population analysed: This analysis population was categorized by race and gender as follows: European American (EA) male n=102, African American (AA) male n=41, EU female n=91, and AA female n=60. Results include measurements at baseline and peak levels of Tumor Necrosis Factor- alpha (TNF-alpha).

1 secondary outcome is reported in the full results.

Adverse events

Time frame: AE data collected for approximately 3.5 years, during the course of all study visits. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Niacin and Endotoxin	0 of 400 (0%)	86 of 400 (21.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30571184Ferguson JF, Xue C, Gao Y, Tian T, Shi J, Zhang X, Wang Y, Li YD, Wei Z, Li M, Zhang H, Reilly MP. Tissue-Specific Differential Expression of Novel Genes and Long Intergenic Noncoding RNAs in Humans With Extreme Response to Evoked Endotoxemia. Circ Genom Precis Med. 2018 Nov;11(11):e001907. doi: 10.1161/CIRCGEN.117.001907.
Derived from this study: PubMed 25579865Ferguson JF, Shah RY, Shah R, Mehta NN, Rickels MR, Reilly MP. Activation of innate immunity modulates insulin sensitivity, glucose effectiveness and pancreatic beta-cell function in both African ancestry and European ancestry healthy humans. Metabolism. 2015 Apr;64(4):513-520. doi: 10.1016/j.metabol.2014.12.007. Epub 2014 Dec 26.
Derived from this study: PubMed 24875672Ferguson JF, Ryan MF, Gibney ER, Brennan L, Roche HM, Reilly MP. Dietary isoflavone intake is associated with evoked responses to inflammatory cardiometabolic stimuli and improved glucose homeostasis in healthy volunteers. Nutr Metab Cardiovasc Dis. 2014 Sep;24(9):996-1003. doi: 10.1016/j.numecd.2014.03.010. Epub 2014 Apr 18.
Derived from this study: PubMed 24504737Liu Y, Ferguson JF, Xue C, Ballantyne RL, Silverman IM, Gosai SJ, Serfecz J, Morley MP, Gregory BD, Li M, Reilly MP. Tissue-specific RNA-Seq in human evoked inflammation identifies blood and adipose LincRNA signatures of cardiometabolic diseases. Arterioscler Thromb Vasc Biol. 2014 Apr;34(4):902-12. doi: 10.1161/ATVBAHA.113.303123. Epub 2014 Feb 6.
Derived from this study: PubMed 23497455Ferguson JF, Patel PN, Shah RY, Mulvey CK, Gadi R, Nijjar PS, Usman HM, Mehta NN, Shah R, Master SR, Propert KJ, Reilly MP. Race and gender variation in response to evoked inflammation. J Transl Med. 2013 Mar 12;11:63. doi: 10.1186/1479-5876-11-63.

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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.

Muredach P Reilly, M.B., MSCE principal investigator

University of Pennsylvania

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Immediate Release Niacin, Extended Release Niacin, Endotoxin in people with Healthy Volunteers, run by University of Pennsylvania 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 24 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 24 Mar 2016. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Mar 2016). 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?

Baseline and Peak TNF-alpha Values as Categorized by Race and Gender (time frame: Baseline (-15 min, -5 min), and 1, 2, 4, 6, 12, 18, and 24 hours post LPS). 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 NCT00953667, which also lists 5 linked publications.

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 24 Mar 2016.