Enteropathy and Diabetes in HIV Patients

Diabetes Clinical Trial

— REEHAD  

Official title:

The Role of Environmental Enteropathy on HIV Associated Diabetes

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03713502
• Other study ID #: TMA2017GSF-1965
• Status: Active, not recruiting
• Start date: May 1, 2019
• Est. completion date: December 30, 2022

Study information

• Verified date: June 2021
• Source: National Institute for Medical Research, Tanzania
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1947
• Est. completion date: December 30, 2022
• Est. primary completion date: December 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Environmental Enteropathy
• HIV
• Intestinal Diseases

Locations

Country	Name	City	State
Tanzania	NIMR Research Clinic	Mwanza	Mwanza Region

Sponsors (4)

Lead Sponsor	Collaborator
National Institute for Medical Research, Tanzania	London School of Hygiene and Tropical Medicine, Queen Mary University of London, University of Copenhagen

Country where clinical trial is conducted

Tanzania, 

References & Publications (9)

Boden G. Free fatty acids, insulin resistance, and type 2 diabetes mellitus. Proc Assoc Am Physicians. 1999 May-Jun;111(3):241-8. Review. — View Citation

Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, Visscher BR, Margolick JB, Dobs AS. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med. 2005 May 23;165(10):1179-84. Erratum in: Arch Intern Med. 2005 Nov 28;165(21):2541. — View Citation

Indulekha K, Anjana RM, Surendar J, Mohan V. Association of visceral and subcutaneous fat with glucose intolerance, insulin resistance, adipocytokines and inflammatory markers in Asian Indians (CURES-113). Clin Biochem. 2011 Mar;44(4):281-7. doi: 10.1016/j.clinbiochem.2010.12.015. Epub 2011 Jan 8. — View Citation

James WP, Coore HG. Persistent impairment of insulin secretion and glucose tolerance after malnutrition. Am J Clin Nutr. 1970 Apr;23(4):386-9. — View Citation

Klatt NR, Funderburg NT, Brenchley JM. Microbial translocation, immune activation, and HIV disease. Trends Microbiol. 2013 Jan;21(1):6-13. doi: 10.1016/j.tim.2012.09.001. Epub 2012 Oct 11. Review. — View Citation

Maganga E, Smart LR, Kalluvya S, Kataraihya JB, Saleh AM, Obeid L, Downs JA, Fitzgerald DW, Peck RN. Glucose Metabolism Disorders, HIV and Antiretroviral Therapy among Tanzanian Adults. PLoS One. 2015 Aug 19;10(8):e0134410. doi: 10.1371/journal.pone.0134410. eCollection 2015. — View Citation

Nazli A, Chan O, Dobson-Belaire WN, Ouellet M, Tremblay MJ, Gray-Owen SD, Arsenault AL, Kaushic C. Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS Pathog. 2010 Apr 8;6(4):e1000852. doi: 10.1371/journal.ppat.1000852. — View Citation

PrayGod G, Changalucha J, Kapiga S, Peck R, Todd J, Filteau S. Dysglycemia associations with adipose tissue among HIV-infected patients after 2 years of antiretroviral therapy in Mwanza: a follow-up cross-sectional study. BMC Infect Dis. 2017 Jan 30;17(1):103. doi: 10.1186/s12879-017-2209-z. — View Citation

Prendergast A, Kelly P. Enteropathies in the developing world: neglected effects on global health. Am J Trop Med Hyg. 2012 May;86(5):756-63. doi: 10.4269/ajtmh.2012.11-0743. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of diabetes	Investigators will determine prevalence of diabetes among participants with enteropathy and those without enteropathy	January 2019 to December 2019
Primary	Prevalence of pre-diabetes	Investigators will determine prevalence of pre-diabetes among participants with enteropathy and those without enteropathy	January 2019 to December 2019