Diabetes Mellitus, Type 2NCT03408678
Determinants of Type 2 Diabetes Risk in Middle-aged Black South African Men and Women
An observational study of Diabetes Mellitus, Type 2 and Insulin Resistance, run by University of Witwatersrand, South Africa at 1 site in South Africa.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 35 to 65 years
- Conditions the study is for
- Diabetes Mellitus, Type 2, Insulin Resistance, Menopause
- How many people
- 1,025 participants
- Where
- 1 siteSouth Africa
- Study dates
- 23 Jan 2017to 31 Jul 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 65 years
- All sexes
- Adult, Older adult
Study population: 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.
Who may be able to join
- Part 1:
- Women on whom baseline data was collected between 2011 and 2014 as part of the Study of Women Entering and in Endocrine Transition.
- Men on whom baseline data was collected in 2014 as part of a larger African genomics study (www.h3Africa.org).
- Part 2: A sub-sample of women from Part 1 of the study:
- Pre-menopausal women age-matched within the age range 35-45 years;
- Post-menopausal women age-matched within the age range 55-65 years;
- All women: BMI 25-40 kg/m2
Who cannot join
- Part 1:
- Failed to consent to participate in the study.
- Part 2:
- Diabetes, thyroid dysfunction, inflammatory, hepatic and renal diseases;
- Use of hormone replacement therapy; hormonal contraceptives, oral cortisone, anti-inflammatory drugs or antiretroviral therapy;
- Peri-menopausal;
- Currently pregnant or lactating;
- Tobacco use.
Trial locations and contacts
1 site in 1 country.
South Africa1 site
SAMRC/WITS Developmental Pathways of Health Research Unit, University of Witwatersrand
Johannesburg, Gauteng, 2013
About this study
Official title: Determinants of Type 2 Diabetes Mellitus Risk in Middle-aged Black South African Men and Women: Dissecting the Role of Sex Hormones, Inflammation and Glucocorticoids
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:
Read more
- 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.
- Does adipose tissue glucocorticoid and inflammatory gene expression differ between pre- and post-menopausal women, with and without HIV, and how do these relate to body fat distribution and insulin sensitivity and secretion?
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).
Read the detailed description
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.
- Conditions
- Diabetes Mellitus, Type 2, Insulin Resistance, Menopause, Hiv
- Keywords
- body composition, glucocorticoids, inflammation, black African, sex, gonadal steroid hormones
- Medical subject headings
- Diabetes Mellitus, Type 2, Insulin Resistance, Acquired Immunodeficiency Syndrome, Inflammation, Coitus
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 4-6 years
Secondary outcomes (1)
Body fat distribution
Body fat depots measured using dual energy x-ray absorptiometry
Measured: 4-6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2018
- Study start23 Jan 2017
- Primary completion31 Jul 2018
- Study completion31 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 1,025 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Witwatersrand, South Africa
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council, South Africa, GlaxoSmithKline, University of Oxford, University Hospital, Umeå
- Responsible party
- Principal investigator, Julia Goedecke, University of Witwatersrand, South Africa
- Investigators
- Julia H Goedecke, PhD, Principal investigator, Medical Research Council, South AfricaLisa K Mickelsfield, PhD, Principal investigator, University of Witwatersrand, South Africa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03408678
- Sponsor's protocol ID
- M160604
- Status last verified
- Jun 2019
- First submitted
- 17 Jan 2018
- Last updated
- 14 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determinants of Type 2 Diabetes Mellitus Risk in Middle-aged Black South African Men and Women: Dissecting the Role of Sex Hormones, Inflammation and Glucocorticoids
- ClinicalTrials.gov ID
- NCT03408678
- Acronym / sponsor ID
- M160604
- Conditions
- Diabetes Mellitus, Type 2, Insulin Resistance, Menopause, Hiv
- Keywords
- body composition, glucocorticoids, inflammation, black African, sex, gonadal steroid hormones
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,025 participants (actual)
- Lead sponsor
- University of Witwatersrand, South AfricaUniversity, hospital or other
- Collaborators
- Medical Research Council, South Africa, GlaxoSmithKline, University of Oxford, University Hospital, Umeå
- Study start
- 23 Jan 2017 (actual)
- Primary completion
- 31 Jul 2018 (actual)
- Study completion
- 31 Jul 2018 (actual)
- First posted
- 24 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- Does adipose tissue glucocorticoid and inflammatory gene expression differ between pre- and post-menopausal women, with and without HIV, and how do these relate to body fat distribution and insulin sensitivity and secretion?
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).
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 35 to 65 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- 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.
Key inclusion criteria (7 listed)
- Women on whom baseline data was collected between 2011 and 2014 as part of the Study of Women Entering and in Endocrine Transition.
- Men on whom baseline data was collected in 2014 as part of a larger African genomics study (www.h3Africa.org).
- Pre-menopausal women age-matched within the age range 35-45 years;
- Post-menopausal women age-matched within the age range 55-65 years;
- All women: BMI 25-40 kg/m2
Key exclusion criteria (8 listed)
- Failed to consent to participate in the study.
- Diabetes, thyroid dysfunction, inflammatory, hepatic and renal diseases;
- Use of hormone replacement therapy; hormonal contraceptives, oral cortisone, anti-inflammatory drugs or antiretroviral therapy;
- Peri-menopausal;
- Currently pregnant or lactating;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Insulin sensitivity and secretion
Time frame: 4-6 years
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
1 secondary outcome
Body fat distribution
Time frame: 4-6 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2019.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julia H Goedecke, PhD principal investigator
Medical Research Council, South Africa
Lisa K Mickelsfield, PhD principal investigator
University of Witwatersrand, South Africa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes Mellitus, Type 2 and Insulin Resistance, run by University of Witwatersrand, South Africa at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin sensitivity and secretion (time frame: 4-6 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2019.