Secondary prevention of type 1 diabetes in children and adolescents aged 6 months - 18 years using oral Vitamin D (calcitriol and analogues)
| ISRCTN | ISRCTN17354692 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN17354692 |
| Secondary identifying numbers | 9/2010 |
- Submission date
- 29/03/2020
- Registration date
- 05/05/2020
- Last edited
- 30/05/2023
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
Many people have blood sugar levels above the normal range, but not high enough to be diagnosed as having diabetes. This is sometimes known as pre-diabetes.
Celiac disease is a condition where the immune system attacks the body’s own tissues when gluten is eaten.
Type 1 diabetes and celiac disease among with other autoimmune diseases may be prevented or regressed using the active hormone calcitriol or it's newer analogs.
Calcitriol is the active form of vitamin D, normally made in the kidney.
The aim of this study is to prove immunomodulating effects of timely administration of calcitriol and analogs for preventing, stopping progression, or succeeding in regression of prediabetes or subclinical Type-1 diabetes in children and adolescents.
Who can participate?
Patients aged six months to 18 years who have been identified as susceptible for type 1 diabetes or celiac disease.
What does the study involve?
Patients are assigned to oral calcitriol or paricalcitol at the highest individually tolerable doses and attend follow-up appointments every 3 - 6 months.
What are the possible benefits and risks of participating?
The main benefit will be to stop and revert seroconversion towards T1D-associated autoimmune targets, restore normal glucose metabolism and possibly acquire positive results regarding abs for celiac disease and hashimoto’s thyroiditis as well.
The main risk is hypercalcemia-hypercalciuria and subsequent possible nephrocalcinosis. That is why all calcium metabolism parameters are carefully monitored with analogous titration of calcitriol/paricalcitol daily doses to prevent any adverse events.
Where is the study run from?
Pediatric Endocrine Clinics (Greece)
When is the study starting and how long is it expected to run for?
June 2010 to January 2030
Who is funding the study?
Pediatric Endocrine Clinics (Greece)
Who is the main contact?
Dr Dimitrios T. Papadimitriou, dtpapadimitriou@pedoendo.gr
Contact information
Scientific
Pediatric Endocrine Clinics
58, av. Kifisias
Athens
15125
Greece
 ORCID ID |
0000-0002-6083-3560 |
|---|---|
| Phone | +30 2103638536 |
| dtpapadimitriou@pedoendo.gr |
Study information
| Study design | Interventional non-randomized |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | No participant information sheet available |
| Scientific title | Secondary PREvention of type 1 diabetes with oral CALcitriol and analogues in children and adolescents aged 6 months - 18 yrs |
| Study acronym | PRECAL |
| Study objectives | The aim of this study is to prove immunomodulating effects of timely administration of calcitriol and analogs for preventing, stopping progression, or succeeding in regression of prediabetes or subclinical Type-1 diabetes in children and adolescents. |
| Ethics approval(s) | Approved 05/01/2010, Athens Medical Center Ethics Committee (Pr. Andreas Fretzayas, Kifisias 58, 15125, Athens Medical Center, Greece, +302106862172, a.fretzayas@iatrikonet.gr), ref: 9/2010 |
| Health condition(s) or problem(s) studied | Susceptibility for Type 1 Diabetes, Prediabetes Type 1, Newly diagnosed (subclinical) Type 1 Diabetes |
| Intervention | In all children aged six months - 18 yrs either at high risk of T1D (at least 1 positive T1D associated autoantibody: IAA, ICA, anti-GAD, anti-IA2) or a predisposing HLA subtype (A, DQ, DR) or diagnosed as prediabetic with an OGTT (using 1.75 gr/Kg oral glucose) showing glucose intolerance (Plasma Glucose > 140 mg/dl at 2hrs in the OGTT) in addition to the above criteria, or as having newly onset subclinical T1D with positive autoantobody(ies) and/or proven HLA susceptibility plus documented pathological OGTT (Glucose > 200 mg/dl at 2hrs) are initiated on oral calcitriol (0.25 mcg x1 up to 0.5 mcg x 3/day) or paricalcitol (1 mcg x 1 up to 24 mcg x 3 /day), as recommended, or MART-10 (when available and at the equivalent dose) while assuring optimal daily cholecalciferol supplementation to achieve 25OHD3 levels > 40-50 ng/ml. Follow-up is every 3-6 months with Calcium metabolism: determination of Ca, P, parathyroid hormone (PTH), alkaline phosphatase (ALP) and total 25(OH)D3 levels, as well as the Ca/creatinine (Cr) ratio in a 2-h morning urine sample, Fasting Plasma Glucose, Insulin and c-peptide as well as HbA1c levels. Individualisation of the highest safe dose of calcitriol/calcitriol analogue accepting a Ca plasma level as high as 11.5 mg/dl and a Ca/Cr 2-hour urine sample as high as 50%. Renal Ultrasound at those with hypercalciuria mandatory every six months. If negativation of auto-abs and regression of prediabetes is achieved, follow-up is extended every 6-12 months with a minimum of 1 year after the achievement of the primary endpoint. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Calcitriol, paricalcitol, MART-10 |
| Primary outcome measure | Measured at follow up every 3 - 6 months from entry into the study until end of study: 1. Type 1 Diabetes associated autoantibodies [Serum levels of islet cell autoantibodies (ICA), autoantibodies to glutamic acid decarboxylase (Gad 65) antigen (anti-GAD65), anti-insulin autoantibodies (IAA), and autoantibodies against protein tyrosine phosphatase IA2 (anti-IA2)] measured using ELISA kits 2. Glucose metabolism (HbA1c, Fasting Glucose, Insulin and c-peptide levels) measured using urine test 3. OGTT response measured using oral glucose tolerance test |
| Secondary outcome measures | Title and prevention or regression of celiac disease autoantibodies, thyroid autoantibodies and other autoimmune diseases if known and applicable measured using ELISA kits at follow up every 3 - 6 months from entry into the study until end of study |
| Overall study start date | 01/01/2010 |
| Completion date | 31/12/2030 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 6 Months |
| Upper age limit | 18 Years |
| Sex | Both |
| Target number of participants | 50 -100 |
| Key inclusion criteria | 1. Age six months - 18 years 2. Positive HLA subtypes for T1D susceptibility 3. At least one positive T1D associated autoantibody 4. Positive HLA or autoantibodies for celiac disease |
| Key exclusion criteria | Already clinically treated T1D on intensified insulin protocols |
| Date of first enrolment | 01/06/2010 |
| Date of final enrolment | 01/01/2030 |
Locations
Countries of recruitment
- Cyprus
- Greece
Study participating centre
Athens
15125
Greece
Sponsor information
Hospital/treatment centre
58, av Kifisias
Athens
15125
Greece
| Phone | +30 2103638536 |
|---|---|
| info@pedoendo.gr | |
| Website | http://www.pedoendo.net |
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | 30/09/2030 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | Early results already published: "Negativation of type 1 diabetes-associated autoantibodies to glutamic acid decarboxylase and insulin in children treated with oral calcitriol" doi: 10.1111/1753-0407.12023 A 10-yr report of the PRECAL study is planned to be published at the end of 2020. |
| IPD sharing plan | All data generated or analysed during this study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 01/09/2013 | 30/03/2020 | Yes | No | |
| Results article | 11/05/2023 | 30/05/2023 | Yes | No |
Editorial Notes
30/05/2023: Publication reference added.
05/05/2020: Trial’s existence confirmed by Athens Medical Center Ethics Committee
