Ignite Creation Date:
2024-05-06 @ 10:58 AM
Last Modification Date:
2024-10-26 @ 12:38 PM
Study NCT ID:
NCT03397966
Status:
TERMINATED
Last Update Posted:
2023-12-15
First Post:
2017-12-20
Brief Title:
Metabolic Effects of Natriuretic Peptide Hormones
Sponsor:
VA Office of Research and Development
Organization:
VA Office of Research and Development
Study Overview
Official Title:
Metabolic Effects of Natriuretic Peptide Hormones
Status:
TERMINATED
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Study drug no longer available
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MENP
Brief Summary:
Accumulating evidence suggests that the natriuretic peptide NP hormonal system has important effects on metabolism However more information is needed to better understand the effects of NPs on metabolism in humans Therefore the investigators propose a study to determine the effects of b-type natriuretic peptide BNP on energy and fat metabolism in humans The investigators primary hypothesis is that the administration of BNP will increase energy expenditure in humans The investigators secondary hypothesis is that BNP administration will promote changes in gene expression in fat tissue suggestive of fat beiging in humans Interventions that safely increase energy expenditure and promote fat beiging represent potential strategies for treating metabolic dysfunction due to obesity
Detailed Description:
Objective The natriuretic peptide NP hormonal system is well-known for its important role in blood pressure regulation However accumulating evidence suggests that the NPs have significant effects on metabolism as well For instance administration of B-type natriuretic peptide BNP to wild-type mice leads to increased energy expenditure changes in gene expression in fat tissue suggestive of fat beiging which may be associated with cardiovascular and metabolic benefits and reduced fat accumulation Although recent studies in rodents suggest that NPs have important metabolic effects there are few prospective data on the metabolic effects of NPs in humans
Therefore the investigators propose a physiologic proof-of-concept study to determine the acute effects of b-type natriuretic peptide BNP on energy and fat metabolism in humans The investigators primary hypothesis is that the administration of BNP will increase energy expenditure in humans The investigators secondary hypothesis is that BNP administration will promote changes in gene expression in adipose tissue suggestive of a beige fat phenotype in humans
Research Plan The investigators propose the following research plan to address the investigators specific aims
Primary Aim To investigate the acute effects of administration of BNP on energy expenditure in humans The investigators propose a randomized placebo-controlled cross-over study in 50 adults 25 lean and 25 obese without significant medical problems Subjects will be randomized to intravenous infusion of recombinant human BNP1-32 or normal saline control with assessment of energy expenditure and other physiologic measures After a 7-day washout period subjects will then undergo the other intervention
Secondary Aim To determine the acute effects of BNP on gene expression in white adipose tissue in humans The investigators will assess markers suggestive of fat beiging in subcutaneous white adipose tissue biopsies after BNP infusion vs control This secondary aim will allow us to explore potential mechanisms underlying the hypothesized changes in energy expenditure
Methods In this cross-over study each subject will receive BNP infusion at one visit and control at the other visit in random order The sequence of the treatments will be randomized There will be a washout period at least 14 days between visits Subjects will be stratified by BMI category lean or obese To address the Primary Aim energy expenditure will be assessed via indirect calorimetry metabolic cart To address the Secondary Aim subcutaneous fat biopsies will be performed and tissue will be analyzed for gene expression of markers suggestive of fat beiging
Clinical Relevance This study will generate novel human data regarding the effects of the NPs on energy metabolism and adipose tissue Interventions that safely increase energy expenditure and promote a beige fat phenotype represent potential strategies for treating obesity-associated metabolic dysfunction The overarching scientific goals of this line of investigation are 1 to elucidate the role of the natriuretic peptide system in cardiometabolic health in humans and 2 to investigate the potential for NP directed therapies in obesity-associated cardiometabolic dysfunction
Update about Study Drug Supply Issues The study started in 72018 and the last time participants were able to receive study drug was in May 2019 due to discontinuation of study drug by the drug manufacturer nesiritide Natrecor Scios LLC after May 2019 Another potential source of drug supply was being sought out by the study team and study recruitment was placed on hold during the search for new potential sources of study drug A new viable source of study drug has not been identified and funding is being closed Thus this study is being terminated Results will be posted for the 5 participants who were able to complete the study procedures prior to the discontinuation of study drug
Therefore the investigators propose a physiologic proof-of-concept study to determine the acute effects of b-type natriuretic peptide BNP on energy and fat metabolism in humans The investigators primary hypothesis is that the administration of BNP will increase energy expenditure in humans The investigators secondary hypothesis is that BNP administration will promote changes in gene expression in adipose tissue suggestive of a beige fat phenotype in humans
Research Plan The investigators propose the following research plan to address the investigators specific aims
Primary Aim To investigate the acute effects of administration of BNP on energy expenditure in humans The investigators propose a randomized placebo-controlled cross-over study in 50 adults 25 lean and 25 obese without significant medical problems Subjects will be randomized to intravenous infusion of recombinant human BNP1-32 or normal saline control with assessment of energy expenditure and other physiologic measures After a 7-day washout period subjects will then undergo the other intervention
Secondary Aim To determine the acute effects of BNP on gene expression in white adipose tissue in humans The investigators will assess markers suggestive of fat beiging in subcutaneous white adipose tissue biopsies after BNP infusion vs control This secondary aim will allow us to explore potential mechanisms underlying the hypothesized changes in energy expenditure
Methods In this cross-over study each subject will receive BNP infusion at one visit and control at the other visit in random order The sequence of the treatments will be randomized There will be a washout period at least 14 days between visits Subjects will be stratified by BMI category lean or obese To address the Primary Aim energy expenditure will be assessed via indirect calorimetry metabolic cart To address the Secondary Aim subcutaneous fat biopsies will be performed and tissue will be analyzed for gene expression of markers suggestive of fat beiging
Clinical Relevance This study will generate novel human data regarding the effects of the NPs on energy metabolism and adipose tissue Interventions that safely increase energy expenditure and promote a beige fat phenotype represent potential strategies for treating obesity-associated metabolic dysfunction The overarching scientific goals of this line of investigation are 1 to elucidate the role of the natriuretic peptide system in cardiometabolic health in humans and 2 to investigate the potential for NP directed therapies in obesity-associated cardiometabolic dysfunction
Update about Study Drug Supply Issues The study started in 72018 and the last time participants were able to receive study drug was in May 2019 due to discontinuation of study drug by the drug manufacturer nesiritide Natrecor Scios LLC after May 2019 Another potential source of drug supply was being sought out by the study team and study recruitment was placed on hold during the search for new potential sources of study drug A new viable source of study drug has not been identified and funding is being closed Thus this study is being terminated Results will be posted for the 5 participants who were able to complete the study procedures prior to the discontinuation of study drug
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CX001678 | OTHER_GRANT | VA CSRD | None |