Ignite Creation Date:
2026-03-26 @ 3:15 PM
Ignite Modification Date:
2026-03-30 @ 9:02 PM
Study NCT ID:
NCT07492550
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-25
First Post:
2026-03-16
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The T1DWATCH Study: a Screening for Type 1 Diabetes Autoantibodies in Children for Early Detection and Intervention.
Sponsor:
Fabiana Sherine Ganem dos Santos
Organization:
Study Overview
Official Title:
T1D WATCH Study, a Comprehensive Screening for Type 1 Diabetes Autoantibodies in Children: A Proactive Approach to Early Detection and Intervention
Status:
NOT_YET_RECRUITING
Status Verified Date:
2026-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
T1DWATCH
Brief Summary:
This study aims to identify early-stage type 1 diabetes (T1D) in children aged 2-6 and 8-10 years through autoantibody (Ab) screening, genetic and immunological analyses, and to evaluate the effectiveness of educational interventions, as well as the feasibility and acceptability of their implementation.
It is a prospective cohort study involving 2,169 children attending primary healthcare centres in the Barcelonès area. Eligible participants will be those engaged in routine paediatric preventive programe with parental informed consent. The screening process consists of three visits: Visit 1: Capillary blood collection for 3 T1D related Ab (3-screen ELISA). Visit 2: Confirmation of positive results through a new venous blood sample to determine single T1D related Ab and metabolic tests (fasting glucose, HbA1c, C-peptide), HLA, imme cell study. Visit 3: Risk stratification based on Ab presence: Group A (negative), Group B (one positive Ab, at risk of T1D), and Group C (two positive Ab, diagnosed at stage 1 or 2). Immunological and metabolic changes will be monitored, and screening effectiveness will be assessed in terms of sensitivity, specificity, and false positive/negative rates. The association between HLA genotype and Ab positivity will be analysed using logistic regression. A cost-effectiveness analysis will be conducted alongside a qualitative evaluation of parents' and stakeholders' perceptions regarding the screening process.This study will provide evidence to optimise early T1D detection and its implementation in primary care.
It is a prospective cohort study involving 2,169 children attending primary healthcare centres in the Barcelonès area. Eligible participants will be those engaged in routine paediatric preventive programe with parental informed consent. The screening process consists of three visits: Visit 1: Capillary blood collection for 3 T1D related Ab (3-screen ELISA). Visit 2: Confirmation of positive results through a new venous blood sample to determine single T1D related Ab and metabolic tests (fasting glucose, HbA1c, C-peptide), HLA, imme cell study. Visit 3: Risk stratification based on Ab presence: Group A (negative), Group B (one positive Ab, at risk of T1D), and Group C (two positive Ab, diagnosed at stage 1 or 2). Immunological and metabolic changes will be monitored, and screening effectiveness will be assessed in terms of sensitivity, specificity, and false positive/negative rates. The association between HLA genotype and Ab positivity will be analysed using logistic regression. A cost-effectiveness analysis will be conducted alongside a qualitative evaluation of parents' and stakeholders' perceptions regarding the screening process.This study will provide evidence to optimise early T1D detection and its implementation in primary care.
Detailed Description:
Detailed Description 12000 characters. :
Type 1 Diabetes Mellitus (T1D) is a chronic autoimmune disease characterized by the destruction of insulin-producing beta cells in the pancreas. The exact cause is not fully understood, involving a combination of genetic predisposition and environmental triggers. Common symptoms include frequent urination, increased thirst, hunger, weight loss, blurred vision, fatigue, and slow wound healing. Currently, there is no known method to prevent T1D, insulin therapy is essential for survival, often administered via injections or insulin pumps. Lifestyle modifications, such as diet and exercise, are also crucial for management. Untreated or poorly managed T1D can lead to serious complications, including diabetic ketoacidosis (DKA), heart disease, kidney failure, and vision problems. Autoantibodies (Ab) play a crucial role in the development and diagnosis of T1D. Ab target various islet cell antigens and are strongly associated with the autoimmune pathogenesis of β-cell destruction. The main Ab related to T1D includes 1. Insulin Ab (IAA), 2. Glutamic acid decarboxylase Ab (GADA), 3. Protein tyrosine phosphatase-like IA-2 Ab (IA-2A), 4. Zinc transporter Antibodies (ZnT8A)6,7. These Abs can appear years before symptoms manifest, indicating an ongoing autoimmune process. The presence of multiple Ab significantly increases the risk of developing T1D. Individuals with two or more positive Ab have a 68% 5-year risk, while those with three Ab have an estimated 100% 5-year risk.
Ab testing is used to distinguish between autoimmune T1D and other forms of diabetes, to identify individuals at risk of developing T1D, or to stage the progression of T1D. A General Hypothesis of this study is that the diagnosis of early-stage Type 1 diabetes (T1D) in children through targeted screening leads to significant clinical benefits by enabling timely intervention to prevent complications, and improved metabolic and psychosocial outcomes.
The specific Hypotheses are:
1. Children at risk of developing T1D can be identified by detecting anti-GAD (GADA), anti-IA2(IA-2A), anti-zinc transporter 8 (ZnT8A), and anti insulin (IAA) antibodies.
2. The presence and levels of these antibodies vary by sex and age, reflecting differences in susceptibility and disease progression.
3. Immune cell populations relevant to immune regulation show distinct patterns in two age groups of children at risk of Type 1 diabetes. These patterns vary by sex and age, indicating early immunological changes associated with early stages of diabetes.
4. Certain HLA genotypes are significantly associated with predisposition to develop T1D, influencing disease onset and progression
5. Educational interventions and staging, followed by enrolment in a monitoring protocol, increase disease awareness, improve self-management skills, and enhance psychosocial well-being in children with early-stage T1D and their parents
6. Screening for early-stage T1D in children is feasible and acceptable among parents, as evidenced by positive feedback on the screening process, educational materials, and overall experience.
7. The implementation of the T1D Watch Study for early detection of T1D through systematic screening is a cost-effective strategy compared to standard clinical diagnosis.
This study aims to identify pre-clinical and clinical stages of T1D in two age groups, young children (from two to six years) and older children (from seven to ten years), and assess the proportion of confirmed cases receiving timely interventions to prevent complications. The specific objectives are:
1. To identify children at risk of developing type 1 diabetes by screening GADA,IA-2A,ZnT8A and IAA associated with increased susceptibility by sex and age.
2. To analyze cell populations relevant to immune regulation to understand early immunological changes in pre diabetes by sex, and two age groups.
3. To analyze the presence of HLA haplotypes of susceptibility to T1D and relate it to other variables (number and titer of antibodies, age of onset ,and clinical results).
4. Evaluate the improvement of the disease awareness, self-management skills, and psychosocial well-being of children (and their parents) who follow educational interventions and enrolment in a monitoring protocol of early-stage Type 1 diabetes.
5. Evaluate the feasibility and acceptability of screening by feedback questionnaires.
6. Analyze the cost-effectiveness of the screening T1D Watch Study
This is a clinical-epidemiological population-based study aimed at identifying preclinical and evaluating the proportion of confirmed cases receiving timely interventions to prevent acute complications at diagnosis. In addition, this study was designed as a prospective cohort that will longitudinally assess immunological and metabolic changes in children at risk of T1D and evaluate the feasibility, acceptability, and educational impact of implementing a population-based screening programme.
The study population consists of 2200 children (boys and girls) aged 2-10 years from three municipalities of Barcelona, Spain. Participants will be recruited from 14 primary care centers (CAPs) in three municipalities in Catalonia, Spain: Badalona Santa Coloma de Gramenet and El Masnou. Follow-up visit to pre-diabetic outcomes will take place at the University Hospital Germans Trias i Pujol. Recruitment and enrolment will be conducted by pediatricians and nurses (HCWs) in Primary Health Centers (PHCs). HCWs will provide written information to the participants who meet the inclusion criteria, and if they are willing to participate, they will be enrolled by signing the informed consent. After this, screening will be conducted on a capillary blood sample (Ab 3-screen ELISA). All the participants enrolled in the study will be called for a visit (visit 1). Only those with a positive result in the Ab 3-screen ELISA, will be called for a second visit and subsequent ones. When the result is negative, it will be recorded in the child's medical history and communicated via health personal app (La Meva Salut). The recruitment period is from 1/5/26 to 31/12/2027 and the Study Period from 1/1/26 to 31/12/2028.
Visit 1 consists of collecting socio-ethnic demographic and clinical data from all participants. Besides, HCWs of PHCs will collect capillary blood using a lancet (250 μL). The test measures three diabetes-related autoantibodies (GADA, IA-2A, ZnT8A) using a validated ELISA method with 95.33% sensitivity and 97.42% specificity46. In 100 participants, both capillary and venous blood will be tested for accuracy. A result ≥20 IU is considered positive and will be communicated to the pediatrician via encrypted email to advise the child to visit 2 Parents will receive results via SMS, and at their next visit, with results also recorded in electronic health records (EHR). Blood samples will be sent to the LCMN. The negative result is recorded in the child's medical history and communicated via La Meva Salut app, ending the child's participation in the T1D WATCH study. If a positive result, the child will be scheduled for a confirmation Visit2. In the follow-up, a new blood sample will be collected to determine the single Ab, and the metabolic test (Basal glucose, HbA1c, C-peptide).Up to 5 mL of blood will be collected, and an additional 4 mL (EDTA sample). Samples will be sent to LCMN within 4 hours, processed, and stored properly. If the initial test is positive (≥20 IU), parents are informed by phone, and the child is invited for Visit 2 to provide a venous blood sample. This sample undergoes further testing, including single ELISA assays for autoantibodies (Ab) (GADA, IA-2A, ZnT8A, and IAA) and confirmation by RBA assay. Additional tests include HLA genotyping and lymphocyte analysis. The diagnosis will be recorded in the child's EHR using the ICD-10 codes for elevated blood glucose and pre-diabetes
Visit 3 aims to stratify early-stage T1D patients. After visit 2, participants will be classified into 3 groups:
* Group A: No Ab. Negative screening test. This result will be recorded in the child's medical history and communicated via the la Meva Salut app, ending the child's participation in the T1D WATCH study.
* Group B (at-risk T1D): Only one positive Ab. Parents of children with a single positive Ab will be contacted at PHCs, offered specific diabetes education, and will receive regular visits with varying frequency depending on age. Under 3 years, every 6 months, and over 3 years, every 12 months. The visit of follow-up includes the monitoring of single antibodies tests, HbA1c, C-peptide, and Glucose
* Group C (Stage 1, 2 T1D): Two positive Ab. The child is diagnosed following ADA and ISPAD guidelines.
Considering the total population of 40.000 children aged from 2 to 10 years in the participating municipalities, an expected antibody prevalence of 2%, ± 0,58% and a 95% confidence level, the required sample size is 2169 individuals. Similar precision could be used around sensibility 95% and Specificity 98%.
Electronic data capture using a specific REDCap for the study. To protect the privacy of our participants, we used cryptography hashtags to anonymize the project database. We also employed the same 10-digit numeric encoding system hosted by REDCap, version 12.4.22 --Vanderbilt University, for the T1D WATCH study.
The T1D WATCH study will generate critical data on the prevalence of pre-symptomatic T1D in Spain, autoantibody patterns, and their correlation with genetic and metabolic markers. The expected contributions include:
1. Improved risk stratification and predictive models for T1D development.
2. Insights into immunological changes during the early stage T1D phase.
3. Assessment of the psychosocial impact of screening and early diagnosis.
4. Evidence supporting future immuno-prevention trials aimed at delaying or preventing T1D onset.
5. Evaluation of the feasibility of integrating screening into routine primary care through the "Programa Creixer amb Salut".
This study evaluates the feasibility and impact of integrating T1D screening into routine pediatric care, focusing on the number of cases diagnosed and its effect on disease control. Rather than being a Type 2 implementation study, which typically assesses strategies to enhance the adoption of evidence-based interventions, this project primarily investigates the clinical and public health implications of early screening. The study will monitor the effectiveness of autoantibody screening in identifying at-risk children and facilitating timely referrals within standard clinical pathways. Newly diagnosed children will be referred to standard clinical pathways for management
Type 1 Diabetes Mellitus (T1D) is a chronic autoimmune disease characterized by the destruction of insulin-producing beta cells in the pancreas. The exact cause is not fully understood, involving a combination of genetic predisposition and environmental triggers. Common symptoms include frequent urination, increased thirst, hunger, weight loss, blurred vision, fatigue, and slow wound healing. Currently, there is no known method to prevent T1D, insulin therapy is essential for survival, often administered via injections or insulin pumps. Lifestyle modifications, such as diet and exercise, are also crucial for management. Untreated or poorly managed T1D can lead to serious complications, including diabetic ketoacidosis (DKA), heart disease, kidney failure, and vision problems. Autoantibodies (Ab) play a crucial role in the development and diagnosis of T1D. Ab target various islet cell antigens and are strongly associated with the autoimmune pathogenesis of β-cell destruction. The main Ab related to T1D includes 1. Insulin Ab (IAA), 2. Glutamic acid decarboxylase Ab (GADA), 3. Protein tyrosine phosphatase-like IA-2 Ab (IA-2A), 4. Zinc transporter Antibodies (ZnT8A)6,7. These Abs can appear years before symptoms manifest, indicating an ongoing autoimmune process. The presence of multiple Ab significantly increases the risk of developing T1D. Individuals with two or more positive Ab have a 68% 5-year risk, while those with three Ab have an estimated 100% 5-year risk.
Ab testing is used to distinguish between autoimmune T1D and other forms of diabetes, to identify individuals at risk of developing T1D, or to stage the progression of T1D. A General Hypothesis of this study is that the diagnosis of early-stage Type 1 diabetes (T1D) in children through targeted screening leads to significant clinical benefits by enabling timely intervention to prevent complications, and improved metabolic and psychosocial outcomes.
The specific Hypotheses are:
1. Children at risk of developing T1D can be identified by detecting anti-GAD (GADA), anti-IA2(IA-2A), anti-zinc transporter 8 (ZnT8A), and anti insulin (IAA) antibodies.
2. The presence and levels of these antibodies vary by sex and age, reflecting differences in susceptibility and disease progression.
3. Immune cell populations relevant to immune regulation show distinct patterns in two age groups of children at risk of Type 1 diabetes. These patterns vary by sex and age, indicating early immunological changes associated with early stages of diabetes.
4. Certain HLA genotypes are significantly associated with predisposition to develop T1D, influencing disease onset and progression
5. Educational interventions and staging, followed by enrolment in a monitoring protocol, increase disease awareness, improve self-management skills, and enhance psychosocial well-being in children with early-stage T1D and their parents
6. Screening for early-stage T1D in children is feasible and acceptable among parents, as evidenced by positive feedback on the screening process, educational materials, and overall experience.
7. The implementation of the T1D Watch Study for early detection of T1D through systematic screening is a cost-effective strategy compared to standard clinical diagnosis.
This study aims to identify pre-clinical and clinical stages of T1D in two age groups, young children (from two to six years) and older children (from seven to ten years), and assess the proportion of confirmed cases receiving timely interventions to prevent complications. The specific objectives are:
1. To identify children at risk of developing type 1 diabetes by screening GADA,IA-2A,ZnT8A and IAA associated with increased susceptibility by sex and age.
2. To analyze cell populations relevant to immune regulation to understand early immunological changes in pre diabetes by sex, and two age groups.
3. To analyze the presence of HLA haplotypes of susceptibility to T1D and relate it to other variables (number and titer of antibodies, age of onset ,and clinical results).
4. Evaluate the improvement of the disease awareness, self-management skills, and psychosocial well-being of children (and their parents) who follow educational interventions and enrolment in a monitoring protocol of early-stage Type 1 diabetes.
5. Evaluate the feasibility and acceptability of screening by feedback questionnaires.
6. Analyze the cost-effectiveness of the screening T1D Watch Study
This is a clinical-epidemiological population-based study aimed at identifying preclinical and evaluating the proportion of confirmed cases receiving timely interventions to prevent acute complications at diagnosis. In addition, this study was designed as a prospective cohort that will longitudinally assess immunological and metabolic changes in children at risk of T1D and evaluate the feasibility, acceptability, and educational impact of implementing a population-based screening programme.
The study population consists of 2200 children (boys and girls) aged 2-10 years from three municipalities of Barcelona, Spain. Participants will be recruited from 14 primary care centers (CAPs) in three municipalities in Catalonia, Spain: Badalona Santa Coloma de Gramenet and El Masnou. Follow-up visit to pre-diabetic outcomes will take place at the University Hospital Germans Trias i Pujol. Recruitment and enrolment will be conducted by pediatricians and nurses (HCWs) in Primary Health Centers (PHCs). HCWs will provide written information to the participants who meet the inclusion criteria, and if they are willing to participate, they will be enrolled by signing the informed consent. After this, screening will be conducted on a capillary blood sample (Ab 3-screen ELISA). All the participants enrolled in the study will be called for a visit (visit 1). Only those with a positive result in the Ab 3-screen ELISA, will be called for a second visit and subsequent ones. When the result is negative, it will be recorded in the child's medical history and communicated via health personal app (La Meva Salut). The recruitment period is from 1/5/26 to 31/12/2027 and the Study Period from 1/1/26 to 31/12/2028.
Visit 1 consists of collecting socio-ethnic demographic and clinical data from all participants. Besides, HCWs of PHCs will collect capillary blood using a lancet (250 μL). The test measures three diabetes-related autoantibodies (GADA, IA-2A, ZnT8A) using a validated ELISA method with 95.33% sensitivity and 97.42% specificity46. In 100 participants, both capillary and venous blood will be tested for accuracy. A result ≥20 IU is considered positive and will be communicated to the pediatrician via encrypted email to advise the child to visit 2 Parents will receive results via SMS, and at their next visit, with results also recorded in electronic health records (EHR). Blood samples will be sent to the LCMN. The negative result is recorded in the child's medical history and communicated via La Meva Salut app, ending the child's participation in the T1D WATCH study. If a positive result, the child will be scheduled for a confirmation Visit2. In the follow-up, a new blood sample will be collected to determine the single Ab, and the metabolic test (Basal glucose, HbA1c, C-peptide).Up to 5 mL of blood will be collected, and an additional 4 mL (EDTA sample). Samples will be sent to LCMN within 4 hours, processed, and stored properly. If the initial test is positive (≥20 IU), parents are informed by phone, and the child is invited for Visit 2 to provide a venous blood sample. This sample undergoes further testing, including single ELISA assays for autoantibodies (Ab) (GADA, IA-2A, ZnT8A, and IAA) and confirmation by RBA assay. Additional tests include HLA genotyping and lymphocyte analysis. The diagnosis will be recorded in the child's EHR using the ICD-10 codes for elevated blood glucose and pre-diabetes
Visit 3 aims to stratify early-stage T1D patients. After visit 2, participants will be classified into 3 groups:
* Group A: No Ab. Negative screening test. This result will be recorded in the child's medical history and communicated via the la Meva Salut app, ending the child's participation in the T1D WATCH study.
* Group B (at-risk T1D): Only one positive Ab. Parents of children with a single positive Ab will be contacted at PHCs, offered specific diabetes education, and will receive regular visits with varying frequency depending on age. Under 3 years, every 6 months, and over 3 years, every 12 months. The visit of follow-up includes the monitoring of single antibodies tests, HbA1c, C-peptide, and Glucose
* Group C (Stage 1, 2 T1D): Two positive Ab. The child is diagnosed following ADA and ISPAD guidelines.
Considering the total population of 40.000 children aged from 2 to 10 years in the participating municipalities, an expected antibody prevalence of 2%, ± 0,58% and a 95% confidence level, the required sample size is 2169 individuals. Similar precision could be used around sensibility 95% and Specificity 98%.
Electronic data capture using a specific REDCap for the study. To protect the privacy of our participants, we used cryptography hashtags to anonymize the project database. We also employed the same 10-digit numeric encoding system hosted by REDCap, version 12.4.22 --Vanderbilt University, for the T1D WATCH study.
The T1D WATCH study will generate critical data on the prevalence of pre-symptomatic T1D in Spain, autoantibody patterns, and their correlation with genetic and metabolic markers. The expected contributions include:
1. Improved risk stratification and predictive models for T1D development.
2. Insights into immunological changes during the early stage T1D phase.
3. Assessment of the psychosocial impact of screening and early diagnosis.
4. Evidence supporting future immuno-prevention trials aimed at delaying or preventing T1D onset.
5. Evaluation of the feasibility of integrating screening into routine primary care through the "Programa Creixer amb Salut".
This study evaluates the feasibility and impact of integrating T1D screening into routine pediatric care, focusing on the number of cases diagnosed and its effect on disease control. Rather than being a Type 2 implementation study, which typically assesses strategies to enhance the adoption of evidence-based interventions, this project primarily investigates the clinical and public health implications of early screening. The study will monitor the effectiveness of autoantibody screening in identifying at-risk children and facilitating timely referrals within standard clinical pathways. Newly diagnosed children will be referred to standard clinical pathways for management
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: