Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05487079 |
| Other study ID # |
RGMN210808 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 17, 2022 |
| Est. completion date |
May 31, 2023 |
Study information
| Verified date |
October 2022 |
| Source |
MRC/UVRI and LSHTM Uganda Research Unit |
| Contact |
Isaac Sekitoleko, MSc |
| Phone |
256701755373 |
| Email |
Isaac.sekitoleko[@]mrcuganda.org |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The true burden of diabetes in sub-Saharan Africa (SSA) is unknown as most of the countries
do not have good quality data. As such, the overall estimate of diabetes prevalence is
largely based on modelled estimates, which may not be accurate.
Additionally, there is lack of clear guidance on which method and thresholds to use in the
diagnosis of diabetes in African populations unlike in high income countries (HIC) where such
guidance is clear. The limited data available shows that diabetes in Africa manifests
differently for example occurring at younger age and in relatively lean individuals.
Moreover, where the oral glucose tolerance test (OGTT) has been used to screen for diabetes,
a significant proportion of individuals have isolated postprandial hyperglycaemia (IPH): The
reasons for this differential manifestation are unclear and the diabetes progression of these
unique phenotypes (for example in terms of risk of complications is unknown or response to
treatment is unknown).
Therefore, the overall aim of this research is to undertake a large study to determine the
true prevalence of diabetes and identify/characterize the different phenotypes; 2) establish
a cohort patients with diabetes to understand the natural course of these different
phenotypes, including how they respond to treatment (i.e. do the IPH or thin diabetics
progress at the same rate as obese, and are the currently used intervention/therapeutic
approaches equally effective in the different phenotypes?).
The collected data is likely to be directly relevant to an improved understanding of the
cause and progression of diabetes, diagnostic test performance, and diabetes care in SSA,
ultimately leading to better patient outcomes and well-being, as well as enhanced
productivity.
Description:
The specific objectives will be to; (1) To determine the true prevalence of diabetes and
prediabetes in a population-based cohort (2) To identify and characterize the different
phenotypes of type 2 diabetes (3) To establish a base-line cohort of well-characterised
people with diabetes to understand disease progression of the different phenotypes, including
uptake and response to treatment. (4) To identify and recruit a cohort of non-diabetic
volunteers (including prediabetes i.e., at high risk of developing diabetes) for longitudinal
follow-up.
Study setting: This will be a population-based survey nested within the General Population
Cohort (GPC). The GPC is a rural population-based cohort study of people living within the 25
villages of Kyamulibwa sub-county of Kalungu District in rural southwest Uganda. The primary
study will be conducted in Uganda. The study shall recruit from 2 sites (rural and urban
areas) across the greater Masaka region in southwest Uganda in order to explore the
differences in lifestyle, and how these influence prevalence of diabetes and its outcomes;
General Population Cohort (GPC) in Kyamulibwa will provide the rural population, and the town
of Lukaya the urban population. Both rural and urban sites are established research areas.
The entire adult population of the GPC will be eligible for this survey. Data from the most
recent Census (2020-2021) in the GPC shows that there are 8,864 adults (aged 18+) of the
total population of 20,751 in Kyamulibwa.
Eligibility: All adults aged 18 years and above will be invited to take part in the study. We
will recruit all adults who are able to provide written informed consent and are residents at
a household (i.e. not a temporary member with intent to leave) in either of the study areas.
Individuals will be excluded from the study based on the following criteria: pregnant women
(can participate six months after childbirth), live outside the geographical sampling frame
for the relevant site or are unable to give informed consent, living outside the relevant
site's catchment area.
Sampling method: This study is powered to estimate the prevalence of diabetes and other
primary outcomes like prediabetes Impaired fasting glycaemia (IFG), isolated postprandial
hyperglycaemia (IPH), isolated-IFG and isolated-Impaired Glucose Tolerance) with sufficient
precision. We have conservatively based our assumptions on results from the 2014 Ugandan
nation-wide cross-sectional survey suggesting that the prevalence of IFG and diabetes in
Uganda is 2% (95% CI: 1.5-2.5%) and 1.4% (95% CI: 0.9 - 1.9%) respectively.3 That survey
detected dysglycaemia using fasting blood glucose alone, rather than OGTT. Applying a rule of
thumb that the margin of error should not exceed 0.25 of the prevalence and based on the
following assumptions: A margin of error of 0.5% (a margin of error of 0.5% to 1% would be
acceptable for low prevalent conditions) and Diabetes prevalence of 5% (assuming OGTT would
detect more cases of diabetes thus doubling the prevalence) and estimated 5% level of
significance (z-value = 1.96). We aim to screen a minimum of 11700 adults across all sites; a
minimum of 5,850 from each site. All the adults in Kyamulibwa- the rural site (8, 864) will
be invited to take part in our survey. For Lukaya-the urban site; initially, 3 of the 5 cells
will be randomly selected and all the adults in the selected cells (approximate total adult
population of 6000) invited to take part in the survey. Recruitment will be restricted to
individuals who reside within defined areas (villages).
Enrollment: This study will consist of overlapping phases as described below:
Phase One: Main baseline survey. This phase comprises the selection and training of survey
team, community sensitisation, obtaining the consent of the study participants, and
conducting the baseline survey. All consented individuals will be interviewed using a
structured pre-tested questionnaire (Data Collection Form) by trained study staff to collect
relevant information including; demographic, socioeconomic and lifestyle in the language
understood by the patient. Thereafter, participants will undergo biophysical measurements
(weight, height, waist and hip circumferences, Mid-upper arm circumference (MUAC) ) and blood
pressure after which they will be invited to come to the research hub in the next days for
blood sample collection after an overnight fast. Participants are required to have fasted for
at least 8 hours and those who have not will be asked to come back another day in a fasting
state. Blood sample collection will be done using standardised procedures. Venous whole blood
will be used for HbA1C, complete blood count, genetics and malaria. Serum will be used for
biochemistry and HIV. NaF blood tube will be used for fasting plasma glucose. hCG urine
testing will be carried out on the urine samples collected.
NB: Those with already clinically diagnosed diabetes and on treatment will come in fasted and
baseline fasting samples taken off. They will not undergo OGTTT.
Phase Two: This phase involves assessment of the reproducibility of diagnostic approaches,
and comparing their general performance. From Phase I of the study, all those with
dysglycaemia (diabetes; prediabetes; i-IFG and i-IGT) and age and sex-matched non-diabetic
subjects (1:1) will be invited back to the research hub for further assessment. In Phase 2,
the aim will be 1) to assess the reproducibility of the diagnostic tests, notably the OGTT;
2) to assess the burden of glycaemia through continuous glucose monitoring; 3) to identify
participants for Phase 3 studies.
Phase Three: This is aimed at assessing and describing any dysglycaemia clusters or
phenotypes by comparing baseline characteristics and evaluating the distribution of various
measures. Further tests may be done in the future to better understand the differences
between the phenotypes. This phase involves utilisation of data generated from phases 1 and 2
to characterise individuals with dysglycaemia further: This is aimed at assessing and
describing any dysglycaemia clusters or phenotypes by comparing baseline characteristics and
evaluating the distribution of various measures inclusive of biochemical parameters (e.g.,
fasting and stimulated C-peptide), adiposity and anthropometric indices, continuous glucose
measures in daily living. Further tests may be done at this level including vascular
complications assessment, endogenous insulin secretion measurement, and exploration of the
inflammatory and immune biomarker (including islet autoantibodies) profiles to better
understand the differences between the phenotypes including Lean versus Non-lean, IPH vs IFG.
Phase Four: Aimed at the creation of well-characterised diabetic and non-diabetic long-term
cohorts. The newly diagnosed diabetes participants will be referred to the local diabetes
clinics where they will be managed according to the Uganda Ministry of health guidelines.
These patients will be followed up in clinics (supported by the research team) to study
natural course, including response to treatment, and disease progression. The non-diabetic
participants will be followed in a longitudinal study nested in the GPC to determine the
incidence of diabetes.
Data collected from the different clinical sites using the data collection form will be
entered into a centralized data management tool (REDCap). All data will be anonymised before
being stored in the data management system.
Ethical consideration: All participants will be required to provide written informed consent
before participating in the study. Refusal to participate will not affect the quality of care
of the participants at the clinical sites. The study has received ethical clearance from the
Uganda Virus Research Institute (GC/127/21/09/858)
