Plain English Summary
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
Trial website
Contact information
Type
Scientific
Primary contact
Dr Dimitrios T. Papadimitriou
ORCID ID
http://orcid.org/0000-0002-6083-3560
Contact details
Pediatric Endocrine Clinics
58
av. Kifisias
Athens
15125
Greece
+30 2103638536
dtpapadimitriou@pedoendo.gr
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
9/2010
Study information
Scientific title
Secondary PREvention of type 1 diabetes with oral CALcitriol and analogues in children and adolescents aged 6 months - 18 yrs
Acronym
PRECAL
Study hypothesis
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
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
Study design
Interventional non-randomized
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
No participant information sheet available
Condition
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
Phase
Phase II
Drug names
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 trial start date
01/01/2010
Overall trial end date
31/12/2030
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
50 -100
Participant exclusion criteria
Already clinically treated T1D on intensified insulin protocols
Recruitment start date
01/06/2010
Recruitment end date
01/01/2030
Locations
Countries of recruitment
Cyprus, Greece
Trial participating centre
Pediatric Endocrine Clinics
58, Kifisias av
Athens
15125
Greece
Sponsor information
Organisation
Pediatric Endocrine Clinics
Sponsor details
58
av Kifisias
Athens
15125
Greece
+30 2103638536
info@pedoendo.gr
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Pediatric Endocrine Clinics
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
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 statement:
All data generated or analysed during this study will be included in the subsequent results publication.
Intention to publish date
30/09/2030
Participant level data
Other
Basic results (scientific)
Publication list
2013 results in https://www.ncbi.nlm.nih.gov/pubmed/23302101 (added 30/03/2020)