Ignite Creation Date:
2024-05-06 @ 7:29 PM
Last Modification Date:
2024-10-26 @ 3:08 PM
Study NCT ID:
NCT06032923
Status:
RECRUITING
Last Update Posted:
2024-07-15
First Post:
2023-09-09
Brief Title:
Double-blind Placebo Controlled Study to Evaluate the Effect of NAD Boosting With Nicotinamide Riboside on Immunometabolism and Immunity in Systemic Lupus Erythematosus
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Double-blind Placebo Controlled Study to Evaluate the Effect of NAD Boosting With Nicotinamide Riboside on Immunometabolism and Immunity in Systemic Lupus Erythematosus
Status:
RECRUITING
Status Verified Date:
2024-09-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Study Description
Systemic lupus erythematosus SLE occurs predominantly in women and is driven by type I interferon dysregulation and neutrophil hyperresponsiveness Neutrophils in females have reduced mitochondrial bioenergetic capacity which affects immunometabolism Nicotinamide adenine dinucleotide NAD boosting with nicotinamide riboside blunts type 1 IFN activation in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects These findings support the proposal of the hypothesis that NAD boosting by NR supplementation will modulate metabolic pathways in lupus and blunt type 1 interferon signaling Moreover as type 1 interferon drives endothelial dysfunction linked to increased cardiovascular risk the effect of NR on endothelial function will be examined
Objectives
Primary Objective Evaluate the effect of NR vs placebo on immunometabolic and inflammatory remodeling in female SLE subjects
Exploratory Objective Compare and characterize myeloid cell bioenergetic and immunometabolic profiles in healthy control and SLE female subjects
Endpoints
Primary Endpoint
The primary end point will be to assess the effect of NR on blunting type I IFN signaling by measuring monocytic secretion of IFN-beta secretion compared to baseline in response to placebo vs NR supplemented in SLE study subjects
Exploratory Endpoints
Healthy control vs SLE subjects
Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in response to activation
Assess cell bioenergetics including 1 monocyte and neutrophil metabolic flux mass spectroscopy of 13C-glucose and 13Cglutamine analysis to investigate their metabolic fates iii Mitochondrial oxygen consumption using glucose amino acid and fatty acid substrates and glycolysis rates
SLE baseline vs NRplacebo supplementation
Baseline vs 6 weeks of NRplacebo
-Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing changes in placebo vs NR groups in monocytes and neutrophils
Baseline vs 12 weeks of NRplacebo
Whole blood NAD levels batched and measured at the end of study enrollment period
Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and chromatin remodeling analysis
Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects
Systemic lupus erythematosus SLE occurs predominantly in women and is driven by type I interferon dysregulation and neutrophil hyperresponsiveness Neutrophils in females have reduced mitochondrial bioenergetic capacity which affects immunometabolism Nicotinamide adenine dinucleotide NAD boosting with nicotinamide riboside blunts type 1 IFN activation in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects These findings support the proposal of the hypothesis that NAD boosting by NR supplementation will modulate metabolic pathways in lupus and blunt type 1 interferon signaling Moreover as type 1 interferon drives endothelial dysfunction linked to increased cardiovascular risk the effect of NR on endothelial function will be examined
Objectives
Primary Objective Evaluate the effect of NR vs placebo on immunometabolic and inflammatory remodeling in female SLE subjects
Exploratory Objective Compare and characterize myeloid cell bioenergetic and immunometabolic profiles in healthy control and SLE female subjects
Endpoints
Primary Endpoint
The primary end point will be to assess the effect of NR on blunting type I IFN signaling by measuring monocytic secretion of IFN-beta secretion compared to baseline in response to placebo vs NR supplemented in SLE study subjects
Exploratory Endpoints
Healthy control vs SLE subjects
Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in response to activation
Assess cell bioenergetics including 1 monocyte and neutrophil metabolic flux mass spectroscopy of 13C-glucose and 13Cglutamine analysis to investigate their metabolic fates iii Mitochondrial oxygen consumption using glucose amino acid and fatty acid substrates and glycolysis rates
SLE baseline vs NRplacebo supplementation
Baseline vs 6 weeks of NRplacebo
-Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing changes in placebo vs NR groups in monocytes and neutrophils
Baseline vs 12 weeks of NRplacebo
Whole blood NAD levels batched and measured at the end of study enrollment period
Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and chromatin remodeling analysis
Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects
Detailed Description:
Study Description
Systemic lupus erythematosus SLE occurs predominantly in women and is driven by type I interferon dysregulation and neutrophil hyper-responsiveness Neutrophils in females have reduced mitochondrial bioenergetic capacity which affects immunometabolism Nicotinamide adenine dinucleotide NAD boosting with nicotinamide riboside blunts type 1 IFN activation in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects These findings support the proposal of the hypothesis that NAD boosting by NR supplementation will modulate metabolic pathways in lupus and blunt type 1 interferon signaling Moreover as type 1 interferon drives endothelial dysfunction linked to increased cardiovascular risk the effect of NR on endothelial function will be examined
Objectives
Primary Objective Evaluate the effect of NR vs placebo on immunometabolic and inflammatory remodeling in female SLE subjects
Exploratory Objective Compare and characterize myeloid cell bioenergetic and immunometabolic profiles in healthy control and SLE female subjects
Endpoints
Primary Endpoint
The primary end point will be to assess the effect of NR on blunting type I IFN signaling by measuring monocytic secretion of IFN-beta secretion compared to baseline in response to placebo vs NR supplemented in SLE study subjects
Exploratory Endpoints
Healthy control vs SLE subjects
Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in response to activation
Assess cell bioenergetics including 1 monocyte and neutrophil metabolic flux mass spectroscopy of 13C-glucose and 13C-glutamine analysis to investigate their metabolic fates iii Mitochondrial oxygen consumption using glucose amino acid and fatty acid substrates and glycolysis rates
SLE baseline vs NRplacebo supplementation
Baseline vs 6 weeks of NRplacebo
-Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing changes in placebo vs NR groups in monocytes and neutrophils
Baseline vs 12 weeks of NRplacebo
Whole blood NAD levels batched and measured at the end of study enrollment period
Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and chromatin remodeling analysis
Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects
Systemic lupus erythematosus SLE occurs predominantly in women and is driven by type I interferon dysregulation and neutrophil hyper-responsiveness Neutrophils in females have reduced mitochondrial bioenergetic capacity which affects immunometabolism Nicotinamide adenine dinucleotide NAD boosting with nicotinamide riboside blunts type 1 IFN activation in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects These findings support the proposal of the hypothesis that NAD boosting by NR supplementation will modulate metabolic pathways in lupus and blunt type 1 interferon signaling Moreover as type 1 interferon drives endothelial dysfunction linked to increased cardiovascular risk the effect of NR on endothelial function will be examined
Objectives
Primary Objective Evaluate the effect of NR vs placebo on immunometabolic and inflammatory remodeling in female SLE subjects
Exploratory Objective Compare and characterize myeloid cell bioenergetic and immunometabolic profiles in healthy control and SLE female subjects
Endpoints
Primary Endpoint
The primary end point will be to assess the effect of NR on blunting type I IFN signaling by measuring monocytic secretion of IFN-beta secretion compared to baseline in response to placebo vs NR supplemented in SLE study subjects
Exploratory Endpoints
Healthy control vs SLE subjects
Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in response to activation
Assess cell bioenergetics including 1 monocyte and neutrophil metabolic flux mass spectroscopy of 13C-glucose and 13C-glutamine analysis to investigate their metabolic fates iii Mitochondrial oxygen consumption using glucose amino acid and fatty acid substrates and glycolysis rates
SLE baseline vs NRplacebo supplementation
Baseline vs 6 weeks of NRplacebo
-Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing changes in placebo vs NR groups in monocytes and neutrophils
Baseline vs 12 weeks of NRplacebo
Whole blood NAD levels batched and measured at the end of study enrollment period
Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and chromatin remodeling analysis
Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 001621-H | None | None | None |