ObesityEarly Phase 1NCT02642523
Natriuretic Peptides and Metabolic Risk in Obesity
A Early Phase 1 study testing Nesiritide, Insulin and Saline in people with Obesity and Hyperinsulinemia, run by Vanderbilt University Medical Center.
Trial summary
The investigators are examining: 1. the relationships of insulin levels and natriuretic peptide hormone levels, and 2. the effects of administering an infusion of natriuretic peptide hormone on the breakdown of fat in healthy lean and otherwise healthy obese individuals. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Hyperinsulinemia
- What is being tested?
- Nesiritide, Insulin and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Start not givento Feb 2017
- Phase
- Early 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women ages 18-50 years
- BMI 18 to <25 kg/m2 (lean group, N=20) or BMI 30 to <40 kg/m2 (obese group, N=20)
Who cannot join
- Current use of antihypertensive medications
- Current use of glucocorticoids, metformin, or any antidiabetes medications
- Prior or current cardiovascular disease, renal disease, or liver disease
- Diabetes mellitus (taking insulin, other anti-diabetic agents, or diet-controlled)
- Atrial fibrillation
- Bleeding disorder or anemia
Show all 10Show fewer
- Elevated LFTs
- estimuated GFR < 60 ml/min
- Abnormal sodium or potassium level
- Positive pregnancy test, women of child-bearing age not practicing birth control, women who are breastfeeding
About this study
The investigators are examining:
- the relationships of insulin levels and natriuretic peptide hormone levels, and
- the effects of administering an infusion of natriuretic peptide hormone on the breakdown of fat in healthy lean and otherwise healthy obese individuals.
Read the detailed description
The cardiac natriuretic peptide hormonal system may protect against the development of cardiometabolic risk. Epidemiologic studies have shown that in relatively healthy individuals without heart failure, low natriuretic peptide levels are associated with unfavorable cardiometabolic phenotypes, including higher blood pressure, obesity, higher insulin levels, and diabetes mellitus. Understanding the mechanisms behind the "natriuretic peptide deficiency" of obesity would illuminate an important way in which obesity interacts with the cardiovascular system.
The investigators propose a prospective cross-over design in 40 healthy lean and otherwise healthy obese individuals. The investigators propose the following specific aims and hypotheses:
Aim 1: To study the effect of hyperinsulinemia on the response of the natriuretic peptide system to salt loading.
Hypothesis 1: Hyperinsulinemia will suppress natriuretic peptide levels in both obese and lean individuals.
Aim 2: To examine the effect of an intravenous infusion of natriuretic peptide on acute markers of lipolysis.
Hypothesis 2: An intravenous infusion of natriuretic peptide will raise acute markers of lipolysis in both obese and lean individuals.
- Conditions
- Obesity, Hyperinsulinemia
- Being tested
- Nesiritide, Insulin, Saline
- Keywords
- natriuretic peptide, insulin, lipolysis, hormones, metabolism
- Medical subject headings
- Obesity, Hyperinsulinism, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NesiritideDrug
Also called Recombinant human BNP
Subjects will receive an intravenous infusion of recombinant human b-type natriuretic peptide (BNP) (Nesiritide) over 2 hours at 2 doses: 0.003 ug/kg/min for 1 hour, followed by 0.01 ug/kg/min for 1 hour. Nesiritide (Johnson and Johnson) is FDA-approved for the treatment of heart failure. Study investigators received approval from the FDA for an IND exemption for nesiritide in this study. While receiving the BNP infusion, subjects will also receive an intravenous infusion of normal (0.9%) saline over 2 hours. Subjects will receive a standardized high-salt diet for at least 6 days prior to this study visit.
InsulinDrug
Also called Human Insulin
The hyperinsulinemic-euglycemic insulin clamp, which will last between 2-2.5 hours, involves continuous intravenous infusions of human regular insulin and of dextrose solution. Simultaneously, subjects receive an intravenous infusion of normal (0.9%) saline over 2 hours. Subjects will receive a standardized high-salt diet for at least 6 days prior to this study visit.
SalineOther
Also called Normal Saline
Subjects will receive an intravenous infusion of normal (0.9%) saline over 2 hours at a rate of 0.25 ml/kg/min. Subjects will receive a standardized high-salt diet for at least 6 days prior to this study visit.
| Study group | Role | What they receive |
|---|---|---|
| Saline Infusion | Placebo comparator | All subjects will undergo 3 interventions, performed at 3 separate outpatient study visits. The order of the 3 interventions will be randomly assigned. The interventions are: Saline Infusion, Insulin Clamp, and BNP Infusion (Nesiritide). Receives: Other: Saline |
| Insulin Clamp | Experimental | All subjects will undergo 3 interventions, performed at 3 separate outpatient study visits. The order of the 3 interventions will be randomly assigned. The interventions are: Saline Infusion, Insulin Clamp, and BNP Infusion (Nesiritide). Receives: Drug: Insulin |
| BNP Infusion (Nesiritide) | Experimental | All subjects will undergo 3 interventions, performed at 3 separate outpatient study visits. The order of the 3 interventions will be randomly assigned. The interventions are: Saline Infusion, Insulin Clamp, and BNP Infusion (Nesiritide). Receives: Drug: Nesiritide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in natriuretic peptide levels
Measured: 4 hours (during 2-hour study infusions and for 2 hours after study infusions)
Change in glycerol levels
Change during 1-hour of low-dose BNP infusion, 1-hour of high-dose BNP infusion, and 1-hour of normal saline infusion
Measured: 1 hour
Secondary outcomes (3)
Change in free fatty acid levels
Change during 1-hour of low-dose BNP infusion, 1-hour of high-dose BNP infusion, and 1-hour of normal saline infusion
Measured: 1 hour
Change in triglyceride levels
Change during 1-hour of low-dose BNP infusion, 1-hour of high-dose BNP infusion, and 1-hour of normal saline infusion
Measured: 1 hour
Change in energy expenditure assessed by indirect calorimetry
Change during 1-hour of low-dose BNP infusion, 1-hour of high-dose BNP infusion, and 1-hour of normal saline infusion
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2015 (estimated)
- Primary completionFeb 2017
- Study completionFeb 2017
Why it stopped: Preliminary data run on rat samples showed that this study question and design would not produce conclusive results. The PI decided not to carry out the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thomas Wang, Vanderbilt University Medical Center
- Investigators
- Katherine N Bachmann, MD, Study director, Vanderbilt Diabetes/EndocrinologyThomas J Wang, MD, Principal investigator, Vanderbilt Cardiovascular Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02642523
- Sponsor's protocol ID
- 151768
- Status last verified
- Oct 2017
- First submitted
- 24 Nov 2015
- Last updated
- 6 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natriuretic Peptides and Metabolic Risk in Obesity
- ClinicalTrials.gov ID
- NCT02642523
- Acronym / sponsor ID
- 151768
- Conditions
- Obesity, Hyperinsulinemia
- Keywords
- natriuretic peptide, insulin, lipolysis, hormones, metabolism
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Preliminary data run on rat samples showed that this study question and design would not produce conclusive results. The PI decided not to carry out the study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Primary completion
- Feb 2017 (actual)
- Study completion
- Feb 2017 (actual)
- First posted
- 30 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators are examining:
- the relationships of insulin levels and natriuretic peptide hormone levels, and
- the effects of administering an infusion of natriuretic peptide hormone on the breakdown of fat in healthy lean and otherwise healthy obese individuals.
Detailed description
The cardiac natriuretic peptide hormonal system may protect against the development of cardiometabolic risk. Epidemiologic studies have shown that in relatively healthy individuals without heart failure, low natriuretic peptide levels are associated with unfavorable cardiometabolic phenotypes, including higher blood pressure, obesity, higher insulin levels, and diabetes mellitus. Understanding the mechanisms behind the "natriuretic peptide deficiency" of obesity would illuminate an important way in which obesity interacts with the cardiovascular system.
The investigators propose a prospective cross-over design in 40 healthy lean and otherwise healthy obese individuals. The investigators propose the following specific aims and hypotheses:
Aim 1: To study the effect of hyperinsulinemia on the response of the natriuretic peptide system to salt loading.
Hypothesis 1: Hyperinsulinemia will suppress natriuretic peptide levels in both obese and lean individuals.
Aim 2: To examine the effect of an intravenous infusion of natriuretic peptide on acute markers of lipolysis.
Hypothesis 2: An intravenous infusion of natriuretic peptide will raise acute markers of lipolysis in both obese and lean individuals.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Saline Infusion | Placebo comparator | Other: SalineAll subjects will undergo 3 interventions, performed at 3 separate outpatient study visits. The order of the 3 interventions will be randomly assigned. The interventions are: Saline Infusion, Insulin Clamp, and BNP Infusion (Nesiritide). |
| Insulin Clamp | Experimental | Drug: InsulinAll subjects will undergo 3 interventions, performed at 3 separate outpatient study visits. The order of the 3 interventions will be randomly assigned. The interventions are: Saline Infusion, Insulin Clamp, and BNP Infusion (Nesiritide). |
| BNP Infusion (Nesiritide) | Experimental | Drug: NesiritideAll subjects will undergo 3 interventions, performed at 3 separate outpatient study visits. The order of the 3 interventions will be randomly assigned. The interventions are: Saline Infusion, Insulin Clamp, and BNP Infusion (Nesiritide). |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Men and women ages 18-50 years
- BMI 18 to <25 kg/m2 (lean group, N=20) or BMI 30 to <40 kg/m2 (obese group, N=20)
Key exclusion criteria (10 listed)
- Current use of antihypertensive medications
- Current use of glucocorticoids, metformin, or any antidiabetes medications
- Prior or current cardiovascular disease, renal disease, or liver disease
- Diabetes mellitus (taking insulin, other anti-diabetic agents, or diet-controlled)
- Atrial fibrillation
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 |
|---|---|---|
| NesiritideAlso: Recombinant human BNPSubjects will receive an intravenous infusion of recombinant human b-type natriuretic peptide (BNP) (Nesiritide) over 2 hours at 2 doses: 0.003 ug/kg/min for 1 hour, followed by 0.01 ug/kg/min for 1 hour. Nesiritide (Johnson and Johnson) is FDA-approved for the treatment of heart failure. Study investigators received approval from the FDA for an IND exemption for nesiritide in this study. While receiving the BNP infusion, subjects will also receive an intravenous infusion of normal (0.9%) saline over 2 hours. Subjects will receive a standardized high-salt diet for at least 6 days prior to this study visit. | Drug | BNP Infusion (Nesiritide) |
| InsulinAlso: Human InsulinThe hyperinsulinemic-euglycemic insulin clamp, which will last between 2-2.5 hours, involves continuous intravenous infusions of human regular insulin and of dextrose solution. Simultaneously, subjects receive an intravenous infusion of normal (0.9%) saline over 2 hours. Subjects will receive a standardized high-salt diet for at least 6 days prior to this study visit. | Drug | Insulin Clamp |
| SalineAlso: Normal SalineSubjects will receive an intravenous infusion of normal (0.9%) saline over 2 hours at a rate of 0.25 ml/kg/min. Subjects will receive a standardized high-salt diet for at least 6 days prior to this study visit. | Other | Saline Infusion |
Primary outcome
Change in natriuretic peptide levels
Time frame: 4 hours (during 2-hour study infusions and for 2 hours after study infusions)
Change in glycerol levels
Time frame: 1 hour
Change during 1-hour of low-dose BNP infusion, 1-hour of high-dose BNP infusion, and 1-hour of normal saline infusion
3 secondary outcomes
Change in free fatty acid levels
Time frame: 1 hour
Change in triglyceride levels
Time frame: 1 hour
Change in energy expenditure assessed by indirect calorimetry
Time frame: 1 hour
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2017.
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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.
Katherine N Bachmann, MD study director
Vanderbilt Diabetes/Endocrinology
Thomas J Wang, MD principal investigator
Vanderbilt Cardiovascular Medicine
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Nesiritide, Insulin and Saline in people with Obesity and Hyperinsulinemia, run by Vanderbilt University Medical Center.
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 2 inclusion and 10 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: withdrawn, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Change in natriuretic peptide levels (time frame: 4 hours (during 2-hour study infusions and for 2 hours after study infusions)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Nov 2017.