An observational study in Diabetes Mellitus, Type 2, Insulin Resistance and Menopause, sponsored by University of Witwatersrand, South Africa. Completed at 1 site in South Africa. Open to participants aged 35 Years to 65 Years. Per ClinicalTrials.gov, last updated 2019-06-14.
Sponsored by University of Witwatersrand, South Africa · Observational
There is little known about menopause in African women, whose phenotype differs to Caucasian women, and no data is available on middle-aged black South African men. Accordingly, the study aims to examine the changes in sex hormone levels over the menopausal transition in women, and in men of the same age, and explore the effects on body fat distribution and insulin sensitivity and secretion, dissecting the specific roles of glucocorticoids and inflammatory mediators, in the context of HIV.
Research questions and hypotheses:
Does the decrease in sex hormones that occur with ageing increase circulating cortisol and/or inflammatory markers, and directly and/or indirectly via increases in central fat mass, decrease insulin sensitivity in middle-aged black South African men and women?
Hypothesis: The mechanism underlying the decrease in insulin sensitivity (outcome) associated with the decline in sex hormones (exposure) that occurs with ageing is mediated via an increase in centralization of body fat (mediator), which is due to an increase in inflammation and cortisol production.
How does HIV alter the relationship between sex hormones, inflammation and cortisol levels, and subsequently body fat distribution and insulin sensitivity?
Hypothesis: HIV infection will exacerbate the effects of the decline in sex hormones with ageing, leading to further increases in inflammation and cortisol production, and a consequent increase in the centralization of body fat and decrease in insulin sensitivity.
Hypothesis: Adipose tissue estrogen receptor beta (ERβ), 11-beta hydroxysteroid dehydrogenase type 1 (11HSD1) activity and pro-inflammatory markers will be higher in post- compared to pre-menopausal women, which will be exacerbated by HIV infection. This will be associated with down-regulation of subcutaneous adipose tissue (SAT) adipogenic genes, increased visceral adipose tissue (VAT), a decrease in insulin sensitivity and secretion, and consequently an increased risk for type 2 diabetes (T2D).
The study will be performed in two parts:
Part 1 - Using a longitudinal design, a sample of 500 black women at different stages of the menopausal transition, and 500 middle-aged men living in Soweto Johannesburg, South Africa, who were included in previous studies between 2011 and 2014, will be recruited. Socio-demographics, health and menopausal status will be assessed using questionnaires; physical activity and sedentary behaviour will be measured using accelerometry; dietary intake will be estimated using a food frequency questionnaire; body composition and body fat distribution will be assessed using dual energy x-ray absorptiometry (DXA); fasting blood samples will be drawn for the determination of cardio-metabolic risk (glucose, insulin, lipids), cluster of differentiation 4 (CD4) count, as well as sex hormones, inflammatory markers and cortisol concentrations. An oral glucose tolerance test will be performed to measure insulin sensitivity and secretion. Statistical analyses will include multilevel mediation modelling.
Part 2 - Using a cross-sectional design, a sub-sample of 100 women from Part 1 will be selected and divided into four groups including 25 pre-menopausal HIV-negative women and 25 age-matched pre-menopausal HIV-positive women (ARV-Naïve); 25 post-menopausal HIV-negative and 25 age-matched post-menopausal HIV-positive women (ARV-Naïve). The women will undergo a frequently sampled intravenous glucose tolerance test to measure insulin sensitivity and secretion, and adipose tissue biopsies will be taken from the gluteal and abdominal SAT depots for the analysis of gene and protein expression relating to inflammation, sex hormones, glucocorticoid metabolism and adipogenesis. Statistical analyses will include multilevel mediation modelling.
10,371 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,406 are open to participants now.
This study's enrollment of 1,025 is above the median of 300 across 1,741 observational studies indexed under Diabetes Mellitus, Type 2.
Browse Diabetes Mellitus, Type 2 studies →University of Witwatersrand, South Africa is the lead sponsor of 47 studies on the registry; 4 are open to participants now.
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A sample of 500 black women at different stages of the menopausal transition, and 500 middle-aged men living in Soweto Johannesburg, South Africa. The women are a sub-sample of 1007 women on whom baseline data was collected between 2011 and 2014 as part of the Study of Women Entering and in Endocrine Transition. The 500 women will be selected using a random process, to allow their profile to mirror that of the overall sample.
The men are a sub-sample of 962 black men on whom similar data was collected in 2014 as part of a larger African genomics study (www.h3africa.org). The 500 men will be randomly selected following the same approach applied to the female cohort.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Part 1:
Part 2: A sub-sample of women from Part 1 of the study:
Exclusion Criteria:
Part 1:
Part 2:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Insulin sensitivity and secretion
Part 1: insulin sensitivity and secretion estimated from an oral glucose tolerance test; Part 2: insulin sensitivity and secretion estimated using a frequently sampled intravenous glucose tolerance test
Time frame: 4-6 years
Body fat distribution
Body fat depots measured using dual energy x-ray absorptiometry
Time frame: 4-6 years
Plan to share: Yes — The principal investigators are prepared to share all individual patient data (IPD) with the wider scientific community, and will make the data available after all the results have been published.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code
Time frame: Starting 6 months after publication of the data.
Access criteria: Access will be assessed on a case-by-case basis by the principal investigators of the study.
No publications or documents are linked to this record.
Ran from Jan 2017 to primary completion in Jul 2018, 18 months.
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This study is completed, as verified in Jun 2019. You cannot join it, but the record below documents what was studied.
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University of Witwatersrand, South Africa