A study to determine the role of genetic differences and environmental exposures as risk factors for dementias and parkinsonism in Nigeria
| ISRCTN | ISRCTN10548575 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10548575 |
| Secondary identifying numbers | 1.0 |
- Submission date
- 03/03/2023
- Registration date
- 07/03/2023
- Last edited
- 06/03/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Environmental exposures and genetic (inherited) factors can increase the risk of developing neurodegenerative disorders. The most prevalent and burdensome of these disorders are Alzheimer's disease and related dementias (ADRD) and Parkinson's disease and atypical parkinsonisms (PDAP). The accompanying disability and increased risk of death indicate a need to find modifiable risk factors that can be incorporated into lifestyles through population-wide strategies. Despite much progress in other populations, very little is known about the contributions of environmental and genetic factors to these conditions in Nigeria and sub-Saharan Africa. This study proposes to address this gap by studying the environmental exposures and genetic differences in persons with ADRD and PDAP, compared to healthy volunteers of similar age, gender, education and ethnicity. The specific individual and combined effects of possible environmental exposures and changes in selected genes will be explored.
Who can participate?
Adults resident in Nigeria and attending clinics at the participating centres who have been diagnosed with dementia or parkinsonism, and healthy volunteers
What does the study involve?
Participants will spend about 2 hours in the clinic and will be asked questions to confirm their diagnosis, undertake a clinical examination and review of any tests they have done, and have a blood sample taken.
What are the possible benefits and risks of participating?
The participants will not have any direct benefit from participating. However, their participation will help find answers that may explain the reasons why people get dementia or parkinsonism. The blood sample will be taken under standard precautions to minimize the pain and risk of infection which are both minimal. In the genetic analysis, the information will be entirely de-identified so that it cannot be linked to any individual participant, and only researchers involved in the study will be able to access the data.
Where is the study run from?
University of Lagos (Nigeria)
When is the study starting and how long is it expected to run for?
November 2019 to December 2023
Who is funding the study?
The Tertiary Education Trust Fund National Research Fund (Nigeria)
Who is the main contact?
Prof. Njideka U. Okubadejo, nokubadejo@unilag.edu.ng
Contact information
Principal Investigator
Department of Medicine
College of Medicine
University of Lagos
Lagos
101012
Nigeria
| Phone | +234 (0)8023130243 |
|---|---|
| nokubadejo@unilag.edu.ng |
Scientific
Department of Medicine
College of Medicine
University of Lagos
Lagos
101012
Nigeria
| Phone | +234 (0)8023130243 |
|---|---|
| nokubadejo@unilag.edu.ng |
Public
Department of Medicine
College of Medicine
University of Lagos
Lagos
101012
Nigeria
| Phone | +234 (0)8110612416 |
|---|---|
| olajide.moyinoluwa@gmail.com |
Study information
| Study design | Prospective observational cross-sectional multicentre study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | Hospital |
| Study type | Screening |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Nationwide study of environmental risk factors and candidate gene-environment interactions in neurodegenerative disorders in Nigeria |
| Study acronym | SERGEND |
| Study objectives | Alzheimer disease and related dementias (ADRD) and Parkinson disease and atypical parkinsonisms (PDAP) represent the two most prevalent and burdensome groups of neurodegenerative disorders globally. Unchecked these disorders will become the leading cause of death by 2050. On account of the apparent complex inheritance for the majority of ADRD and PDAP, an interplay between heritability and environmental exposures is presumed to underpin the mechanisms leading to progressive and selective neuronal cell loss and subsequent pathological and clinical manifestations. There is a significant gap in the specifics of the genetic variability predisposing to ADRD and PDAP, and the precise environmental exposures in diverse populations are largely unknown. Elucidating environmental risk factors and a detailed understanding of the interaction with genetic factors are critical steps for understanding the mechanistic basis of ADRD and PDAP, and for driving the development of interventions to prevent, treat and reduce the unacceptable accompanying morbidity and mortality. Identifying the genetic and environmental factors responsible for variability in the risk of developing ADRD and PDAP will also help identify persons and individual characteristics that portend increased susceptibility, and guide developing interventions to forestall such exposures, particularly if modifiable. Considering the variety of environmental exposures encountered based on geographical location, and the disparity in prevalence and incidence of ADRD and PDAP between African and more industrialized countries, it is imperative that the role of environmental exposures and potential interaction with genetic variability as protective or causative factors is explored. The environmental risk factors and gene-environment interactions for ADRD and PDAP in Nigeria (and indeed in sub-Saharan Africa) have not been systematically studied from a national and geographically diverse and representative perspective. This study proposes to bridge this gap in knowledge by utilizing a case (affected) – control (unaffected) approach to systematically evaluate the effects of several putative environmental exposures and genetic variability in two candidate genes, on the risk of ADRD and PDAP in Nigerians. The study will explore the individual and combined effects (gene-environment interactions) of the environmental and genetic susceptibility risk factors in ADRD and PDAP risk. The candidate genes (α synuclein – SNCA and apolipoprotein E – APOE) have been selected for their prior strong association with ADRD and PDAP). |
| Ethics approval(s) | Approved 31/03/2020, National Health Research Ethics Committee (National Health Research Ethics Committee, Department of Health Planning, Research and Statistics, Federal Ministry of Health, 11th Floor, Federal Secretariat Complex Phase III, Ahmadu Bello Way, Abuja, Nigeria; +234 (0)95238367; +234 (0)8063190328; chairman@nhrec.net), ref: NHREC/01/01/2007 |
| Health condition(s) or problem(s) studied | Neurodegenerative diseases (Alzheimer's disease and related dementias (ADRD); Parkinson's disease and atypical parkinsonism (PDAP)) |
| Intervention | Study participants (persons with ADRD and PDAP) will be recruited from participating hospitals across the six geopolitical zones of Nigeria under the guidance of study neurologists. All dementia cases will be screened with the Intervention for Dementia in Elderly Africans (IDEA) questionnaire as an initial step, and then further evaluated with relevant components of the National Alzheimer Coordinating Centre (NACC) Unified Dementia Screening instrument (version 3.0) (UDS). Parkinsonism will be diagnosed based on the UKPDS brain bank criteria and additional features in atypical cases. Controls will be healthy (neurologically normal) age- and gender-matched unrelated persons from the same population. Standardized clinical assessments will be conducted to characterize disease, evaluate severity and document environmental risk factors (using the common data elements from the NIH environmental risk factor questionnaire. Baseline anthropometric indices, fasting blood glucose and brain imaging (where previously available as part of the ongoing clinical consultation) will be documented. Blood samples (whole blood) will be obtained for genotyping. |
| Intervention type | Mixed |
| Primary outcome measure | The association between each specified environmental risk factor documented in the Environmental Risk Questionnaire (ERQ) (residential history, smoking and tobacco, alcohol use, diet, occupation, toxicants, pesticides, caffeine, head injury, NSAID and calcium channel blocker use) and genetic polymorphisms in SNCA REP1 and APOE and ADRD and PDAP will be measured by comparing the presence of the risk factor compared in cases (dementia i.e. ADRD, and parkinsonism i.e. PDAP) and controls. Specifically, the study will report on: 1. Relative risk associated with specified environmental exposures in dementia versus healthy controls 2. Relative risk associated with specified environmental exposures in parkinsonism versus healthy controls 3. Hazard ratios comparing the frequency of APOE polymorphisms in cases (dementia and parkinsonism) and controls 4. Hazard ratios comparing the frequency of SNCA REP1 polymorphisms in cases (dementia and parkinsonisms) and controls. 1. Environmental risk exposure measured using Environmental Risk Questionnaire at baseline (enrolment) 2. Genetic variability in APOE and SNCA REP1 measured using genotyping for polymorphic variability/allele frequencies at baseline (enrolment) |
| Secondary outcome measures | Combined effects (gene-environment interactions) will be analysed by comparing the combined effects of all environmental risk factors and the genetic polymorphisms (measured at baseline [enrolment]) on the risk of dementia and parkinsonism. Computational analysis will be employed as the statistical method for data analysis. The outcomes will be reported as risk ratios. |
| Overall study start date | 01/11/2019 |
| Completion date | 31/12/2023 |
Eligibility
| Participant type(s) | Mixed |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 3000 |
| Key inclusion criteria | 1. ADRD or PDAP diagnosed based on standardized clinical research criteria (with or without corroborating additional diagnostic information) 2. Neurologically healthy volunteers |
| Key exclusion criteria | 1. Non-consent 2. Unable to complete clinical assessments due to disability |
| Date of first enrolment | 01/05/2020 |
| Date of final enrolment | 31/12/2023 |
Locations
Countries of recruitment
- Nigeria
Study participating centres
Lagos
-
Nigeria
Zaria
-
Nigeria
Maiduguri
-
Nigeria
Ilorin
-
Nigeria
Ibadan
-
Nigeria
Enugu
-
Nigeria
Calabar
-
Nigeria
Lagos
-
Nigeria
Makurdi
-
Nigeria
Owerri
-
Nigeria
Sponsor information
Government
No 6 Zambezi Crescent Maitama
Abuja
-
Nigeria
| Phone | +234 (0)8008383863 |
|---|---|
| NRF_STI@tetfund.gov.ng | |
| Website | https://tetfund.gov.ng/index.php/annual-intervention/national-research-fund/ |
Funders
Funder type
Government
Government organisation / Local government
- Alternative name(s)
- Tertiary Education Trust Fund, TETFund
- Location
- Nigeria
Results and Publications
| Intention to publish date | 01/12/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in high-impact peer reviewed journals |
| IPD sharing plan | The datasets generated during and/or analyzed during the current study will be available upon request from Prof. Njideka Okubadejo (nokubadejo@unilag.edu.ng): deidentified data including baseline demographics and summary data on the presence or absence of risk factors in the Environmental Risk Factor Questionnaire. Written informed consent was obtained from all participants. Only anonymized data will be shared. |
Editorial Notes
06/03/2023: Trial's existence confirmed by the Tertiary Education Trust Fund.
