Determinants of Cardiovascular Disease, Kidney Disease and Diabetes
NCT ID: NCT04646408
Last Updated: 2020-11-30
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
UNKNOWN
Total Enrollment
400 participants
Study Classification
OBSERVATIONAL
Study Start Date
2020-10-01
Study Completion Date
2022-10-01
Brief Summary
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Cardiovascular disease (CVD), chronic kidney disease (CKD), diabetes mellitus (DM) and HIV infection are long-term conditions (LTC) with major health implications for people of African ancestry. These LTC often arise in the setting of an adverse demographic, social, biologic and genetic environment, although this remains poorly understood.
The investigators plan to conduct a comprehensive syndemic evaluation in individuals with and without CVD, CKD and DM in people of African ancestry with HIV to obtain novel insights into the development of LTC in this population. In addition, the investigators will conduct focus groups to explore the role of syndemic factors in the development of LTC and develop and pilot an educational programme to improve knowledge about LTC in the African/Caribbean community.
The investigators plan to conduct a comprehensive syndemic evaluation in individuals with and without CVD, CKD and DM in people of African ancestry with HIV to obtain novel insights into the development of LTC in this population. In addition, the investigators will conduct focus groups to explore the role of syndemic factors in the development of LTC and develop and pilot an educational programme to improve knowledge about LTC in the African/Caribbean community.
Detailed Description
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Black African/Caribbean Communities in South London are disproportionally affected by long-term conditions (LTC), with a higher prevalence and an earlier onset (by about 13 years) (1). This population experiences high rates of hypertension, obesity, diabetes mellitus (DM), chronic kidney disease (CKD), cardiovascular disease (CVD) including stroke, social deprivation, poor housing, and mental health conditions such as anxiety and depression (1). HIV infection is also considerably more common in Black African/Caribbean Communities in South London than in the general UK population (2,3) and gives rise to stigma and discrimination, low self-esteem, dysfunctional relationships and loneliness (4).
The relationship between hypertension, obesity, metabolic syndrome, diabetes mellitus and CKD is well recognised. In this population, 'hypertensive nephropathy' is about 10-fold more common than in Caucasians, with earlier onset of end stage kidney disease (ESKD) (5). Although hypertensive nephropathy in people of African ancestry was previously attributed to resistant hypertension, exacerbated by poor engagement with health care services and suboptimal adherence to antihypertensive therapy, there is emerging evidence of strong genetic susceptibility to CKD as a result of prevalent mutations in the apolipoprotein L1 (APOL1), glutathione-S-transferase-μ1 (GSTM1) genes or sickle cell trait (SCT) (6-12). However, despite their strong associations with CKD, many individuals with these genetic variants do not develop kidney disease, suggesting that additional (i) biologic (e.g. coinfections, inflammation), (ii) environmental factors (e.g. obesity, diabetes), and (iii) socio-economic aspects, (e.g. inadequate health care access, stigma) may contribute to the development or progression of CKD although this has not been well studied.
There is growing recognition of the important role of social determinants of health (SDH) and its impact across a wide range of health indicators, settings, and populations (13,14). The World Health Organization (WHO) refers to SDH as conditions to which people are born, grow, work, live and age, linked to personal circumstances and systems (e.g. social, economic and political policies/heath care systems) that influences their daily lives (15-16). The new conceptual framework of syndemics provide an opportunity to study diseases and health conditions in populations that are deepened by the social, economic, environmental and political environment of a given population (17). The definition of a syndemic is 'the presence of two or more disease states (anchored around a core disease, in our case HIV) that adversely interact with each other, negatively affecting the mutual course of each disease trajectory, enhance vulnerability, and which are more harmful by experienced inequities' (18). This approach of a so-called 'syndemic lens' may be helpful in our study to identify the associations between genetic, biologic and social factors that contribute to the development of CKD and DM in people with hypertension, obesity, sub-clinical CKD and/or metabolic syndrome. This systemic approach can offer a new understanding of diseases that can improve public health and treat individual patients at the same time (19).
South London has a large (\>200,000) population of African and Caribbean ancestry who are disproportionally affected by HIV and experience a higher burden of CKD, DM and other LTC, often with earlier onset compared to white populations. The investigators aim to study the demographic, clinical, social and genetic factors that associate with CKD, DM and multiple LTC in people with HIV. CKD and DM are key LTC that associate with hypertension, obesity and cardiovascular disease, resulting in or contribute to functional impairment, polypharmacy and impaired bio-psycho-social health outcomes.
The HIV clinics in South London provide a unique opportunity to access a diverse African and Caribbean population of working age in whom LTC can be studied. People with HIV from black African/Caribbean communities experience a high degree of social and economic deprivation, stigma, anxiety and depression which are considered important syndemic factors in the development of LTC. CKD and DM are common LTC, highly relevant to the black population, and relatively early events in the development of multiple and disabling LTC, thus identifying a population for targeted interventions that may reduce the rate of progression from a single to multiple LTC.
HIV infection, itself a LTC, can be effectively controlled with antiretroviral therapy, affording normal life expectancy and interrupting onward transmission. Routine care includes 6-12 monthly assessments for other LTCs, providing opportunities for recruitment of well characterised populations unselected for specific co-morbid conditions.
No studies to date in the UK have examined the contribution of biologic, clinical, social and genetic factors to the development of LTC in African/Caribbean populations with HIV to date. The team will generate detailed information on factors that associate with CKD, DM, CVD and multiple LTC as well as hypertension, sub-clinical CKD, obesity and insulin resistance, which often precede the development of CKD, DM and other LTC in this population. This study is likely to identify novel associations which can be confirmed and further explored in subsequent studies of HIV positive and general African/Caribbean populations. Stored biological samples will allow us to explore pathogenetic mechanisms in subsequent studies.
Key barriers to uptake of existing and novel interventions include low literacy levels, low perception of quality of life, lack of knowledge of LTCs, etc. The investigators will explore how best to overcome these barriers in focus groups and develop a culturally sensitive educational programme, aiming to reach individuals in communities that tend to poorly engage with health care and preventive programmes.
The relationship between hypertension, obesity, metabolic syndrome, diabetes mellitus and CKD is well recognised. In this population, 'hypertensive nephropathy' is about 10-fold more common than in Caucasians, with earlier onset of end stage kidney disease (ESKD) (5). Although hypertensive nephropathy in people of African ancestry was previously attributed to resistant hypertension, exacerbated by poor engagement with health care services and suboptimal adherence to antihypertensive therapy, there is emerging evidence of strong genetic susceptibility to CKD as a result of prevalent mutations in the apolipoprotein L1 (APOL1), glutathione-S-transferase-μ1 (GSTM1) genes or sickle cell trait (SCT) (6-12). However, despite their strong associations with CKD, many individuals with these genetic variants do not develop kidney disease, suggesting that additional (i) biologic (e.g. coinfections, inflammation), (ii) environmental factors (e.g. obesity, diabetes), and (iii) socio-economic aspects, (e.g. inadequate health care access, stigma) may contribute to the development or progression of CKD although this has not been well studied.
There is growing recognition of the important role of social determinants of health (SDH) and its impact across a wide range of health indicators, settings, and populations (13,14). The World Health Organization (WHO) refers to SDH as conditions to which people are born, grow, work, live and age, linked to personal circumstances and systems (e.g. social, economic and political policies/heath care systems) that influences their daily lives (15-16). The new conceptual framework of syndemics provide an opportunity to study diseases and health conditions in populations that are deepened by the social, economic, environmental and political environment of a given population (17). The definition of a syndemic is 'the presence of two or more disease states (anchored around a core disease, in our case HIV) that adversely interact with each other, negatively affecting the mutual course of each disease trajectory, enhance vulnerability, and which are more harmful by experienced inequities' (18). This approach of a so-called 'syndemic lens' may be helpful in our study to identify the associations between genetic, biologic and social factors that contribute to the development of CKD and DM in people with hypertension, obesity, sub-clinical CKD and/or metabolic syndrome. This systemic approach can offer a new understanding of diseases that can improve public health and treat individual patients at the same time (19).
South London has a large (\>200,000) population of African and Caribbean ancestry who are disproportionally affected by HIV and experience a higher burden of CKD, DM and other LTC, often with earlier onset compared to white populations. The investigators aim to study the demographic, clinical, social and genetic factors that associate with CKD, DM and multiple LTC in people with HIV. CKD and DM are key LTC that associate with hypertension, obesity and cardiovascular disease, resulting in or contribute to functional impairment, polypharmacy and impaired bio-psycho-social health outcomes.
The HIV clinics in South London provide a unique opportunity to access a diverse African and Caribbean population of working age in whom LTC can be studied. People with HIV from black African/Caribbean communities experience a high degree of social and economic deprivation, stigma, anxiety and depression which are considered important syndemic factors in the development of LTC. CKD and DM are common LTC, highly relevant to the black population, and relatively early events in the development of multiple and disabling LTC, thus identifying a population for targeted interventions that may reduce the rate of progression from a single to multiple LTC.
HIV infection, itself a LTC, can be effectively controlled with antiretroviral therapy, affording normal life expectancy and interrupting onward transmission. Routine care includes 6-12 monthly assessments for other LTCs, providing opportunities for recruitment of well characterised populations unselected for specific co-morbid conditions.
No studies to date in the UK have examined the contribution of biologic, clinical, social and genetic factors to the development of LTC in African/Caribbean populations with HIV to date. The team will generate detailed information on factors that associate with CKD, DM, CVD and multiple LTC as well as hypertension, sub-clinical CKD, obesity and insulin resistance, which often precede the development of CKD, DM and other LTC in this population. This study is likely to identify novel associations which can be confirmed and further explored in subsequent studies of HIV positive and general African/Caribbean populations. Stored biological samples will allow us to explore pathogenetic mechanisms in subsequent studies.
Key barriers to uptake of existing and novel interventions include low literacy levels, low perception of quality of life, lack of knowledge of LTCs, etc. The investigators will explore how best to overcome these barriers in focus groups and develop a culturally sensitive educational programme, aiming to reach individuals in communities that tend to poorly engage with health care and preventive programmes.
Conditions
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Cardiovascular Diseases
Diabetes Mellitus
Chronic Kidney Diseases
Keywords
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chronic kidney disease
cardiovascular disease
HIV
syndemic
diabetes
Study Design
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Observational Model Type
OTHER
Study Time Perspective
CROSS_SECTIONAL
Study Groups
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Participants with CKD
Recruitment is from a cohort of HIV positive individuals of African ancestry with Chronic Kidney Disease CKD defined as eGFR \<60 mL/min/1.73m2, and/or albumin/creatinine ratio \>30 mg/mmol or protein/creatinine ratio \>50 mg/mmol Anticipated n=75
No interventions assigned to this group
Participants with diabetes
Recruitment is from a cohort of HIV positive individuals of African ancestry with diabetes. Diabetes is defined as being on diabetic medications or HbA1c \>48 mmol/mol.
Anticipated n=75
No interventions assigned to this group
Participants with ischaemic heart disease/stroke
Recruitment is from a cohort of HIV positive individuals of African ancestry with previous ischaemic heart disease or stroke Anticipated n=50
No interventions assigned to this group
No CKD/DM/CVD cohort
Recruitment is from a cohort of HIV positive individuals of African ancestry who do not have CKD, diabetes or prior ischaemic heart disease/stroke.
Anticipated n=200
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
1. Having previously participated in the GEN-AFRICA study
2. Aged 18-60 years
2. Aged 18-60 years
Exclusion Criteria
1. Not having participated in the GEN-AFRICA study
2. Aged \>60 years
2. Aged \>60 years
Minimum Eligible Age
18 Months
Maximum Eligible Age
60 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
Yes
Sponsors
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King's College Hospital NHS Trust
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Locations
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King's College London
London, Apartment G02, Cordage House, United Kingdom
Site Status
RECRUITING
Countries
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United Kingdom
Central Contacts
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Facility Contacts
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Rachel Hung, MSc
Role: primary
Frank Post, PhD
Role: backup
References
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1. GSTT Charity report: From one to many. Exploring people's progression to multiple longterm conditions in an urban environment. Guy's and St. Thomas' Charity, London, July 2018. p10. 2. Public Health England. HIV in the UK 2016 report.
Reference Type
BACKGROUND
2. Public Health England. HIV in the UK 2016 report. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment _data/file/602942/HIV_in_the_UK_report.pdf
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BACKGROUND
3. Public Health England. Hepatitis B in London 2016 data. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment _data/file/801174/London_hepatitis_B_report_2016.pdf
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BACKGROUND
4. Public Health England. Positive Voices: The National Survey of People Living with HIV. Findings from the 2017 Survey. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/857922/PHE_positive_voices_report_2019.pdf
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BACKGROUND
Saran R, Li Y, Robinson B, Abbott KC, Agodoa LY, Ayanian J, Bragg-Gresham J, Balkrishnan R, Chen JL, Cope E, Eggers PW, Gillen D, Gipson D, Hailpern SM, Hall YN, He K, Herman W, Heung M, Hirth RA, Hutton D, Jacobsen SJ, Kalantar-Zadeh K, Kovesdy CP, Lu Y, Molnar MZ, Morgenstern H, Nallamothu B, Nguyen DV, O'Hare AM, Plattner B, Pisoni R, Port FK, Rao P, Rhee CM, Sakhuja A, Schaubel DE, Selewski DT, Shahinian V, Sim JJ, Song P, Streja E, Kurella Tamura M, Tentori F, White S, Woodside K, Hirth RA. US Renal Data System 2015 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2016 Mar;67(3 Suppl 1):Svii, S1-305. doi: 10.1053/j.ajkd.2015.12.014. No abstract available.
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Kopp JB, Nelson GW, Sampath K, Johnson RC, Genovese G, An P, Friedman D, Briggs W, Dart R, Korbet S, Mokrzycki MH, Kimmel PL, Limou S, Ahuja TS, Berns JS, Fryc J, Simon EE, Smith MC, Trachtman H, Michel DM, Schelling JR, Vlahov D, Pollak M, Winkler CA. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol. 2011 Nov;22(11):2129-37. doi: 10.1681/ASN.2011040388. Epub 2011 Oct 13.
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BACKGROUND
Tin A, Scharpf R, Estrella MM, Yu B, Grove ML, Chang PP, Matsushita K, Kottgen A, Arking DE, Boerwinkle E, Le TH, Coresh J, Grams ME. The Loss of GSTM1 Associates with Kidney Failure and Heart Failure. J Am Soc Nephrol. 2017 Nov;28(11):3345-3352. doi: 10.1681/ASN.2017030228. Epub 2017 Jul 18.
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BACKGROUND
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BACKGROUND
Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL, Bernhardy AJ, Hicks PJ, Nelson GW, Vanhollebeke B, Winkler CA, Kopp JB, Pays E, Pollak MR. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010 Aug 13;329(5993):841-5. doi: 10.1126/science.1193032. Epub 2010 Jul 15.
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BACKGROUND
Naik RP, Derebail VK, Grams ME, Franceschini N, Auer PL, Peloso GM, Young BA, Lettre G, Peralta CA, Katz R, Hyacinth HI, Quarells RC, Grove ML, Bick AG, Fontanillas P, Rich SS, Smith JD, Boerwinkle E, Rosamond WD, Ito K, Lanzkron S, Coresh J, Correa A, Sarto GE, Key NS, Jacobs DR, Kathiresan S, Bibbins-Domingo K, Kshirsagar AV, Wilson JG, Reiner AP. Association of sickle cell trait with chronic kidney disease and albuminuria in African Americans. JAMA. 2014 Nov 26;312(20):2115-25. doi: 10.1001/jama.2014.15063.
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Naik RP, Irvin MR, Judd S, Gutierrez OM, Zakai NA, Derebail VK, Peralta C, Lewis MR, Zhi D, Arnett D, McClellan W, Wilson JG, Reiner AP, Kopp JB, Winkler CA, Cushman M. Sickle Cell Trait and the Risk of ESRD in Blacks. J Am Soc Nephrol. 2017 Jul;28(7):2180-2187. doi: 10.1681/ASN.2016101086. Epub 2017 Mar 9.
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Other Identifiers
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KingCKD
Identifier Type: -
Identifier Source: org_study_id