Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06638177
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
None
First Post:
2024-10-07
Brief Title:
Obesity and Obesity-Related Factors and Risk of Herpes Zoster Shingles and Postherpetic Neuralgia
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Obesity and Obesity-Related Factors and Risk of Herpes Zoster and Postherpetic Neuralgia
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The investigators objectives are to examine the longitudinal association of obesity and obesity-related factors and risk of incident herpes zoster HZ also known as shingles and the longitudinal association of obesity and obesity-related factors and risk of developing post-herpetic neuralgia PHN among those with HZ The investigators propose to examine more refined assessments of adiposity leveraging the resources of several large-scale ongoing cohort studies of women and men with decades of follow-up and rich health-related data including multiple validated anthropomorphic measures medical history dietary intake and lifestyle factors The investigators will also examine existing data on plasma adipokines cytokines and plasma metabolomics The investigators will use the Nurses Health Study NHS I Nurses Health Study II NHS II and the Health Professionals Follow-up Study HPFS total Ngt200000 to prospectively investigate whether obesity and obesity-related factors influence the risk of developing HZ The investigators have already identified gt30000 cases of incident HZ among the 3 cohorts reported with high validity and information on HZ continues to be collected In addition the investigators obtained detailed information on HZ course complications including PHN treatment and other related factors on a Zoster Supplemental Questionnaire ZSQ administered to those participants in the NHS I and II who reported shingles on the main questionnaires n10123 to date The investigators will also administer the ZSQ to newly identified HZ cases identified on the 2023 NHS I and NHS II biennial questionnaires No previous study has investigated the longitudinal relation between adiposity and risk of post-herpetic neuralgia PHN This study could provide important new insight into how obesity and obesity-related factors influence the risk of HZ and the risk of developing PHN among individuals with HZ and how alterations in circulating metabolites and metabolic pathways including those that are obesity-related are associated with risk of developing HZ and PHN
Detailed Description:
Research Questions Hypotheses
1 The investigators hypothesize that greater body adiposity is associated with increased risk of developing herpes zoster HZ Specifically the investigators hypothesize that higher body mass index BMI larger waist circumference and higher waist to hip ratio waist to height ratio predicted fat mass predicted percent fat and ABSI are associated with increased risk of developing HZ The investigators will also examine whether these associations differ by age sex and other factors
2 The investigators hypothesize that plasma biomarkers of obesity and of inflammation are independently and longitudinally associated with risk of HZ Specifically The investigators hypothesize that lower plasma total and high-molecular-weight HMW adiponectin and higher plasma leptin IL-6 and CRP are independently associated with higher risk of HZ
3 The investigators hypothesize that greater body adiposity is associated with increased risk of developing postherpetic neuralgia PHN Specifically The investigators hypothesize that higher body mass index larger waist circumference and higher waist to hip ratio waist to height ratio predicted fat mass predicted percent fat and ABSI are associated with increased risk of developing post-herpetic neuralgia PHN among those who develop HZ
4 The investigators hypothesize that obesity-related metabolic dysregulation contributes to HZ risk Specifically The investigators hypothesize that circulating levels of metabolites and metabolic pathways that are altered by adiposity and may influence cell-mediated immune function such as glutamine arginine the branched chain amino acids isoleucine leucine and valine the tryptophan metabolite kynurenine and certain fatty acids such as lysophosphatidylcholines are associated with risk of developing HZ
5 The investigators hypothesize that obesity-related metabolic dysregulation contributes to risk of developing PHN among women with HZ Specifically the investigators hypothesize that alterations of plasma levels of certain metabolites and metabolic pathways previously implicated in chronic neuroimmune inflammation and increased neurosensitivity including abnormal fatty acid and amino acid metabolism eg arachidonic acid derived eicosanoids glutamate-aspartate tryptophan-kynurenine and arginine-ornithine metabolic pathways are associated with the development of PHN among women with HZ
III Objectives
A Objective 1a To examine whether anthropomorphic measures of obesity from early through middle and later adult life are independently and longitudinally associated with risk of HZ The investigators will use information on BMI waist circumference hip circumference predicted fat mass and percent fat ABSI and HZ that has been longitudinally collected across the lifespan among gt200000 women and men WThe investigators e hypothesize that higher body mass index BMI larger waist circumference higher waist to hip ratio higher waist to height ratio higher predicted fat mass predicted percent fat and ABSI are associated with increased risk of developing HZ The investigators will also examine whether these associations differ by age sex and other factors
B Objective 1b To examine whether plasma biomarkers of obesity the immunomodulatory adipokines leptin and adiponectin and markers of inflammation interleukin-6 IL-6 and C-reactive protein CRP are independently and longitudinally associated with risk of HZ Using existing plasma biomarker information from gt19000 participants including over 2500 that developed HZ after the time of the blood collection incident HZ the investigators will examine associations of these plasma biomarkers and risk of developing HZ and examine whether the proposed association between obesity and HZ risk is mediated through immunomodulatory adipokines or inflammation The investigators hypothesize that lower total and high-molecular-weight HMW adiponectin and higher plasma leptin IL-6 and CRP are independently associated with higher risk of HZ
C Objective 1c To investigate whether anthropomorphic measures of obesity are associated with higher risk of developing postherpetic neuralgia PHN among women with HZ In a substudy of over 10000 NHS I and NHS II participants who reported a history of shingles the investigators collected detailed information on HZ course treatment and related complications on a Zoster Supplemental Questionnaire ZSQ Information on PHN was validated by medical record review The investigators hypothesize that higher body mass index larger waist circumference and higher waist to hip ratio waist to height ratio predicted fat mass predicted percent fat and ABSI are associated with increased risk of developing PHN
D Objective 2a To assess how obesity-related metabolic dysregulation contributes to HZ risk
The investigators will conduct an agnostic analysis to identify individual metabolites and metabolic pathways associated with obesity among gt13000 women and men for whom the investigators have comprehensive information on plasma metabolomics profiles The investigators hypothesize that circulating levels of metabolites and metabolic pathways that are altered by body adiposity and may influence cell-mediated immune function such as glutamine arginine the branched chain amino acids isoleucine leucine and valine the tryptophan metabolite kynurenine and certain fatty acids such as lysophosphatidylcholines are associated with risk of developing HZ The investigators will create a metabolite-based obesity score and assess the degree to which the association between obesity and HZ risk is mediated by the metabolite-based obesity score Secondarily the investigators will conduct an agnostic investigation to identify individual metabolites and metabolic pathways associated with risk of developing HZ
E Objective 2b To assess how obesity-related metabolic dysregulation contributes to risk of developing postherpetic neuralgia PHN among women with HZ Among participants who had HZ and completed the Zoster Supplementary Questionnaire ZSQ that collected additional details about HZ course complications and treatment and for whom information on metabolomics information is available n1005 to date the investigators will assess the degree to which the potential association between obesity and PHN risk is mediated by the metabolite-based obesity score developed in Aim 2a above Secondarily the investigators will conduct an agnostic investigation to identify individual metabolites and metabolic pathways associated with risk of developing PHN The investigators hypothesize that alterations of plasma levels of certain metabolites and metabolic pathways previously implicated in chronic neuroimmune inflammation and increased neurosensitivity including abnormal fatty acid and amino acid metabolism eg arachidonic acid derived eicosanoids glutamate-aspartate tryptophan-kynurenine and arginine-ornithine metabolic pathways are involved in the development of PHN among women with HZ
1 The investigators hypothesize that greater body adiposity is associated with increased risk of developing herpes zoster HZ Specifically the investigators hypothesize that higher body mass index BMI larger waist circumference and higher waist to hip ratio waist to height ratio predicted fat mass predicted percent fat and ABSI are associated with increased risk of developing HZ The investigators will also examine whether these associations differ by age sex and other factors
2 The investigators hypothesize that plasma biomarkers of obesity and of inflammation are independently and longitudinally associated with risk of HZ Specifically The investigators hypothesize that lower plasma total and high-molecular-weight HMW adiponectin and higher plasma leptin IL-6 and CRP are independently associated with higher risk of HZ
3 The investigators hypothesize that greater body adiposity is associated with increased risk of developing postherpetic neuralgia PHN Specifically The investigators hypothesize that higher body mass index larger waist circumference and higher waist to hip ratio waist to height ratio predicted fat mass predicted percent fat and ABSI are associated with increased risk of developing post-herpetic neuralgia PHN among those who develop HZ
4 The investigators hypothesize that obesity-related metabolic dysregulation contributes to HZ risk Specifically The investigators hypothesize that circulating levels of metabolites and metabolic pathways that are altered by adiposity and may influence cell-mediated immune function such as glutamine arginine the branched chain amino acids isoleucine leucine and valine the tryptophan metabolite kynurenine and certain fatty acids such as lysophosphatidylcholines are associated with risk of developing HZ
5 The investigators hypothesize that obesity-related metabolic dysregulation contributes to risk of developing PHN among women with HZ Specifically the investigators hypothesize that alterations of plasma levels of certain metabolites and metabolic pathways previously implicated in chronic neuroimmune inflammation and increased neurosensitivity including abnormal fatty acid and amino acid metabolism eg arachidonic acid derived eicosanoids glutamate-aspartate tryptophan-kynurenine and arginine-ornithine metabolic pathways are associated with the development of PHN among women with HZ
III Objectives
A Objective 1a To examine whether anthropomorphic measures of obesity from early through middle and later adult life are independently and longitudinally associated with risk of HZ The investigators will use information on BMI waist circumference hip circumference predicted fat mass and percent fat ABSI and HZ that has been longitudinally collected across the lifespan among gt200000 women and men WThe investigators e hypothesize that higher body mass index BMI larger waist circumference higher waist to hip ratio higher waist to height ratio higher predicted fat mass predicted percent fat and ABSI are associated with increased risk of developing HZ The investigators will also examine whether these associations differ by age sex and other factors
B Objective 1b To examine whether plasma biomarkers of obesity the immunomodulatory adipokines leptin and adiponectin and markers of inflammation interleukin-6 IL-6 and C-reactive protein CRP are independently and longitudinally associated with risk of HZ Using existing plasma biomarker information from gt19000 participants including over 2500 that developed HZ after the time of the blood collection incident HZ the investigators will examine associations of these plasma biomarkers and risk of developing HZ and examine whether the proposed association between obesity and HZ risk is mediated through immunomodulatory adipokines or inflammation The investigators hypothesize that lower total and high-molecular-weight HMW adiponectin and higher plasma leptin IL-6 and CRP are independently associated with higher risk of HZ
C Objective 1c To investigate whether anthropomorphic measures of obesity are associated with higher risk of developing postherpetic neuralgia PHN among women with HZ In a substudy of over 10000 NHS I and NHS II participants who reported a history of shingles the investigators collected detailed information on HZ course treatment and related complications on a Zoster Supplemental Questionnaire ZSQ Information on PHN was validated by medical record review The investigators hypothesize that higher body mass index larger waist circumference and higher waist to hip ratio waist to height ratio predicted fat mass predicted percent fat and ABSI are associated with increased risk of developing PHN
D Objective 2a To assess how obesity-related metabolic dysregulation contributes to HZ risk
The investigators will conduct an agnostic analysis to identify individual metabolites and metabolic pathways associated with obesity among gt13000 women and men for whom the investigators have comprehensive information on plasma metabolomics profiles The investigators hypothesize that circulating levels of metabolites and metabolic pathways that are altered by body adiposity and may influence cell-mediated immune function such as glutamine arginine the branched chain amino acids isoleucine leucine and valine the tryptophan metabolite kynurenine and certain fatty acids such as lysophosphatidylcholines are associated with risk of developing HZ The investigators will create a metabolite-based obesity score and assess the degree to which the association between obesity and HZ risk is mediated by the metabolite-based obesity score Secondarily the investigators will conduct an agnostic investigation to identify individual metabolites and metabolic pathways associated with risk of developing HZ
E Objective 2b To assess how obesity-related metabolic dysregulation contributes to risk of developing postherpetic neuralgia PHN among women with HZ Among participants who had HZ and completed the Zoster Supplementary Questionnaire ZSQ that collected additional details about HZ course complications and treatment and for whom information on metabolomics information is available n1005 to date the investigators will assess the degree to which the potential association between obesity and PHN risk is mediated by the metabolite-based obesity score developed in Aim 2a above Secondarily the investigators will conduct an agnostic investigation to identify individual metabolites and metabolic pathways associated with risk of developing PHN The investigators hypothesize that alterations of plasma levels of certain metabolites and metabolic pathways previously implicated in chronic neuroimmune inflammation and increased neurosensitivity including abnormal fatty acid and amino acid metabolism eg arachidonic acid derived eicosanoids glutamate-aspartate tryptophan-kynurenine and arginine-ornithine metabolic pathways are involved in the development of PHN among women with HZ
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None