Clinical trial NCT03713502: Enteropathy and Diabetes in HIV Patients
Official title: The Role of Environmental Enteropathy on HIV Associated Diabetes
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Diabetes
Environmental Enteropathy
HIV
Keywords: Pre-diabetes
Diabetes
HIV
Enteropathy
Inflammation
Microbial translocation
Endotoxin translocation
Insulin resistance
Visceral obesity
Incretin hormones
GLP-1
GLP-2
GIP
Lead sponsor: National Institute for Medical Research, Tanzania
Sponsor class: OTHER_GOV
Collaborators: name: University of Copenhagen
name: London School of Hygiene and Tropical Medicine
name: Queen Mary University of London
First posted: 2018-10-19
Enrollment: 1947
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be recruited from HIV-infected patients attending antiretroviral therapy (ART) clinics in Mwanza (Tanzania) as well as from the general population (those who meet the inclusion criteria).

Brief summary: Emerging data suggest that HIV-infected people have disproportionately higher risk of diabetes than HIV-uninfected people. Multiple factors may contribute to elevated diabetes risk including increased prevalence of conventional non-communicable diseases (NCDs) risk factors, use of some antiretroviral drugs regimens, and inflammation and immune activation secondary to environmental- and HIV-enteropathy. To date, enteropathy has been little studied in relation to HIV and diabetes in Sub-Saharan Africa. Enteropathy leads to systemic inflammation which may in turn result in insulin resistance and may reduce secretion of incretins, the gut hormones which stimulate synthesis and secretion of insulin. Both mechanisms could potentially result in higher diabetes risk in HIV patients. This study investigates the hypothesis that among HIV-infected patients environmental enteropathy increase the risk of diabetes. The findings of this study will provide information which could be used as a basis for developing clinical trials to address different aspects of environmental enteropathy in order to reduce the burden of diabetes among HIV-infected populations

Detailed description: This study will investigate if enteropathy is associated with higher risk of diabetes in HIV patients using a cross-sectional study design. To implement it cost-efficiently, investigators will nest it to an ongoing cohort study which investigates risk factors for diabetes and other chronic diseases among HIV patients in Tanzania (the CICADA study) (NCT03106480).

The CICADA study recruited 1947 participants during 2016/2017. These will be followed- up during 2017/2018 and 2018/2019 by which point it is expected that about 1550 participants will be retained in the cohort. Data collection for the current study will coincide with the final CICADA study follow-up. Data on demography, socio-economic status, conventional non-communicable disease risk factors, HIV and TB status, antiretroviral therapy use history, anthropometry, body composition, lipid profile, CD4 count, C-reactive protein, alpha-1-acid glycoprotein, insulin, and diabetes status will be retrieved from CICADA study. Data on gut enteropathy biomarkers i.e plasma citrulline, GLP-1, glucagon like peptide-2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP), fecal myeloperoxidase (MPO), neopterin, and alpha-1-antitrypsin, intestinal permeability (by 4-sugar test), lipopolysaccharide binding protein, tumor necrosis factor-α receptor, interleukin 6, and fecal elastase (as an indicator of pancreatic function) will be collected solely for this study to investigate the study hypothesis.

Data will be entered in Cspro and managed and analysed in STATA. Both linear and logistic regression will be used to assess the associations between exposure variables (markers of enteropathy) and outcome (diabetes). In addition, causal inference techniques will be used to investigate associations between enteropathy biomarkers and diabetes.

Eligibility criteria: Inclusion Criteria: Participants who were recruited in CICADA study (NCT03106480) during 2016/2017 and meet the following criteria:

* Aged 18 years or above
* HIV-infected
* HIV-uninfected
* Resident of Mwanza region
* Consent to take part in this study

Exclusion Criteria:

* None

Primary outcomes:
measure: Prevalence of diabetes
timeFrame: January 2019 to December 2019
measure: Prevalence of pre-diabetes
timeFrame: January 2019 to December 2019
Secondary outcomes:
Other outcomes:
Locations:
city: Mwanza
country: Tanzania
facility: NIMR Research Clinic
state: Mwanza Region
Study officials:
affiliation: National Institute for Medical Research
name: Dr George PrayGod, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Copenhagen
name: Dr Daniel Faurholt-Jepsen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: London School of Hygiene and Tropical Medicine
name: Prof Suzanne Filteau, PhD
role: PRINCIPAL_INVESTIGATOR
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