Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05361148 |
| Other study ID # |
EPPHZU29 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 12, 2021 |
| Est. completion date |
October 31, 2024 |
Study information
| Verified date |
April 2022 |
| Source |
London School of Hygiene and Tropical Medicine |
| Contact |
Suzanne Filteau, PhD |
| Phone |
+442079588108 |
| Email |
Suzanne.Filteau[@]lshtm.ac.uk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Whilst there is an increasing prevalence of overweight and obesity worldwide, malnutrition
remains common. In addition, malnutrition, overweight, and infections often interact. The
consequences of malnutrition after birth are little studied. Severe acute malnutrition in
childhood remains common in Africa and Asia and many adult patients with tuberculosis or HIV,
diseases which are common in Africa and Asia, may become malnourished. We are interested in
diabetes, which in Africa and Asia affects people at younger age and lower weight than in
Europe. There is evidence that severe postnatal malnutrition increases the risk of later
diabetes but the evidence is piecemeal and there is little information as to the mechanisms
involved. It is thus difficult to determine what treatments or preventative strategies are
appropriate.
We wish to focus on the pancreas which is a key organ in digestion and metabolic processes,
especially in relation to diabetes. We will investigate pancreas size, microscopic structure,
hormone and digestive enzyme production, and the body's response to these hormones among
groups of people in Tanzania, Zambia, India and the Philippines. These groups have
participated in the research team's previous studies of malnutrition and were malnourished
before birth, as children, or as adults. They now live in places with a wide range of access
to foods high in fat and sugar which could affect their risk of diabetes. We will compare
their pancreas function to that of never-malnourished controls at each site. We will use
advanced statistical methods to understand the links between early malnutrition and later
diabetes, taking into account the factors often associated with diabetes such as age, current
overweight and infection.
Even if we find no important link between early malnutrition and later diabetes, the research
will lead to improved understanding of the long-term consequences of malnutrition and the
presentation and underlying metabolism of diabetes in Africa and Asia. Thus, the project will
lead to improved health care for both malnourished and diabetic people.
Description:
Prenatal growth retardation is associated with increased risk of adult chronic
non-communicable diseases (NCDs) including diabetes. However, there is limited information
regarding how postnatal malnutrition, in childhood or adulthood, affects these risks. The
question of long-term effects of postnatal malnutrition is of increasing importance, because,
with improved care, more children survive severe acute malnutrition and, amongst adults, drug
treatments for infections, e.g. HIV and tuberculosis which frequently cause or are associated
with malnutrition (MALN), have improved patient survival. Our project will focus on the role
of the pancreas in the long-term consequences of MALN since both its endocrine and exocrine
functions are critical for nutrition and NCDs. There is evidence that pancreatic functions
may not recover fully after childhood or adult MALN and that the phenotype of diabetes in
countries with prevalent MALN differs from that in high-income countries.
Overall hypothesis:
Severe malnutrition (MALN) at any age has medium- and long-term detrimental effects on
endocrine and exocrine pancreatic function and structure.
Study design and population: Cross-sectional observational study recruiting a total of 3700
participants from previous/ongoing observational cohorts in: Zambia (1 adult (N=300) and 1
adolescent cohort (N=180)), Tanzania (1 adult cohort (N=1400)), Philippines (2 adult cohorts
N=600/N=420), India (1 adolescent low birth weight cohort N=800))
Specific objective 1: To determine if MALN earlier in life is associated with abnormalities
of pancreas structure and function.
Hypothesis 1: Prior MALN is associated with later abnormal pancreatic structure and endocrine
and exocrine function.
Approach: We will follow up individuals from the above cohorts in which there are
participants, all now adolescents or adults, who suffered from MALN at different stages
earlier in life as well as age- and sex-matched individuals who have never been malnourished
as a comparison. We will assess in those with and without prior MALN:
1. blood glucose, insulin and C-peptide during an oral glucose tolerance test (OGTT)
2. haemoglobin A1c (HbA1c)
3. faecal elastase and plasma lipase as exocrine pancreas markers
4. pancreas size and architecture using ultrasound and computed tomography (CT) (subset)
Specific objective 2: To investigate whether pancreatic abnormalities in participants with
prior MALN and diabetes are compatible with a previously prescribed entity of fibro-calculous
diabetes.
Hypothesis 2: Prior MALN is associated with pancreatic calcifications and is common in those
with diabetes.
Approach: We will conduct CT scans to investigate pancreatic calcification among non-pregnant
adult study participants.
Specific objective 3: To investigate the relative importance of decreased insulin production
or increased insulin resistance in MALN associated with concurrent infections in African and
Asian adult populations.
Hypothesis 3: The abnormal glucose regulation seen after MALN and infection is associated
with relative insulin deficiency with or without insulin resistance.
Approach: This hypothesis will be investigated within the Tanzanian cohort and one Filipino
adult cohort, both of whom had MALN associated with infection. We will select 20 men and 20
women from each of two groups (MALN and non-MALN) in each cohort based on whether or not in
our prior research we recorded them as experiencing MALN. In these participants we will:
1. Measure in blood samples collected at 0, 15, 30, 45, 60, 90 and 120 minutes during an
OGTT: glucose, insulin, C-peptide (all time points), the incretins gastric inhibitory
polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) and glucagon at 0, 30, 60, 90 and
120 minutes, and proinsulin and trypsinogen at baseline only;
2. Conduct intravenous glucose tolerance tests (IVGTT) and measure in blood samples
collected at -10, -1, 2, 4, 6, 8, 10 minutes: glucose, insulin, and C-peptide.
Specific objective 4: To investigate whether a prior abnormal pro-insulin / insulin ratio is
associated with diabetes in adults infected with HIV or previously with tuberculosis.
Hypothesis 4: An abnormal pro-insulin/insulin ratio is associated with later development of
diabetes in adults who had MALN and infection.
Approach: For participants from the CICADA, Tanzania, cohort we have fasting plasma samples
stored from prior follow-ups up to 10 years earlier. Glucose has already been measured in
these samples as well as insulin in some samples. We will measure insulin in the remaining
stored samples and proinsulin in all to investigate whether prior proinsulin / insulin ratio
is associated with subsequent diabetes.
