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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.


Recruitment information / eligibility

Status Recruiting
Enrollment 3700
Est. completion date October 31, 2024
Est. primary completion date April 30, 2024
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 8 Years to 90 Years
Eligibility Inclusion Criteria: - member of one of the 6 included cohorts - informed consent (for children, informed assent and consent of guardian) Exclusion Criteria: - lack of consent - pregnant women and chidlren will be excluded from CT scans and interavenous glucose tolerance tests

Study Design


Intervention

Other:
no interventions will be used
This is a cohort study with no interventions.

Locations

Country Name City State
India Institute of Home Economics Delhi University Delhi
Philippines Nutrition Centre of the Philippines Cebu City
Tanzania National Institute for Medical Research Mwanza
Zambia University Teaching Hospital Lusaka

Sponsors (7)

Lead Sponsor Collaborator
London School of Hygiene and Tropical Medicine Delhi University, National Institute for Medical Research, Tanzania, Newcastle University, UK, Nutrition Centre of the Philippines, University of Copenhagen, University Teaching Hospital, Lusaka, Zambia

Countries where clinical trial is conducted

India,  Philippines,  Tanzania,  Zambia, 

Outcome

Type Measure Description Time frame Safety issue
Primary Pancreas endocrine function Mathematical modelling of blood glucose, insulin and C-peptide at 3 (for children) or 7 (for adults) times during a 120 minute oral glucose tolerance test (OGTT) to determine first and second phase insulin release and insulin resistance 1 year
Primary Pancreas exocrine function faecal elastase and plasma lipase 1 year
Secondary Pancreas size and structure pancreas size and architecture using ultrasound and computed tomography (CT) (subset) 1 year
Secondary pancreatic calcification calcification determined by CT scan (subset) 1 year
Secondary Hemoglobin A1c blood HbA1c as diabetes marker 1 year
Secondary insulin production and insulin resistance (in-depth study in a subset) Mathematical modelling of data from analytes from an intravenous glucose tolerance tests (IVGTT) in a subset and measure in blood samples collected at -10, -1, 2, 4, 6, 8, 10 minutes: glucose, insulin, and C-peptide Combined results will be used to indicate first and second phase insulin production and insulin resistance. 1 year
Secondary gastrointestinal contribution to glucose metabolism and diabetes Incretins (gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)) and glucagon at 0, 30, 60, 90 and 120 minutes during an OGTT 1 year
Secondary Proinsulin proinsulin in baseline samples before OGTT 1 year
Secondary abnormal prior pro-insulin/insulin ratio and diabetes (subset) From CICADA cohort, measurement of pro-insulin and insulin in samples collected 4 years previously and compare with current diabetes by OGTT 1 year
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