Condition category
Nutritional, Metabolic, Endocrine
Date applied
29/03/2020
Date assigned
05/05/2020
Last edited
05/05/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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

http://www.pedoendo.net

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)

Publication citations

Additional files

Editorial Notes

05/05/2020: Trial’s existence confirmed by Athens Medical Center Ethics Committee