- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04838145
The Diabetes Virus Detection and Intervention Trial (DiViDInt)
April 6, 2021 updated by: Lars Krogvold, Oslo University Hospital
A randomized, double-blind, placebo-controlled study in 96 children and adolescents age 6-15 newly diagnosed with type 1 diabetes to describe the influence of antiviral treatment (Pleconaril and Ribavirin) on progression of disease and residual insulin secretion.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
If antiviral treatment is efficient in halting the disease progression, it will be to great benefit for the participating patients.
Maintenance or even an increase in beta cell mass due to regeneration will lead to improved endogenous insulin production and give a milder course of the disease with improved glycemic control.
This will in a substantial way improve the long-term prognosis with less severe long term vascular complications.Some patients may have close to complete remission and be able to stop insulin treatment.
If antiviral treatment is effective, it would add proof to the concept that type 1 diabetes in its origin is a viral disease.
This would be an important milestone in medical research and a breakthrough in the understanding of the etiopathogenesis of autoimmune diseases.
It may promote the development of vaccines to prevent the disease.
T1D seems more aggressive in children than in adults, and the beta cell function decline rapidly compared to adults.
As a consequence, the effect of antiviral treatment will potentially be more significant in children than in adults.
Children have higher HbA1c which increases the risk of complications.
Thus, T1D is a more aggressive disease in children than in adults and hence it's important to do this study in children.
Pharmaceuticals are usually studied in different age intervals, commonly 1-6 years, 6-12 years and 12-15 years.
For safety reasons and simplicity, the investigators want to start with the two older groups.
The investigators will treat the participants with two antiviral medications (Pleconaril and ribavirin) or placebo in a double blind, randomized, placebo controlled, parallel group study.
Pleconaril has previously been given in doses of 5-10mg/kg x 2-3 in clinical trials in children, thus achieving serum levels high enough for killing the majority of the viruses.
The investigators have, due to the long treatment period, reduced the doses to 5 mg/kg x 2. Ribavirin will be given in dosages according to Summariy of product characteristics (SmPC).
The investigators have chosen to administer Investigational Medicinal Product (IMPs) as an oral solution as this will make it easier to give the medication according to weight.
Study Type
Interventional
Enrollment (Actual)
96
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Oslo, Norway, 0514
- Pediatric department, Oslo University Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
6 years to 15 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Diagnosed type 1 Diabetes (E10.9). First injection of insulin maximum three weeks prior to inclusion.
- Must be willing and capable of taking the study drugs and meet for tests and follow up as described.
- Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to International Conference on Harmonization Good Clinical Practice (ICH GCP), and national/local regulations.
- Aged 6.00-15.99 years at inclusion
Exclusion Criteria:
- Treatment with any oral or injected anti-diabetic medications other than insulin.
- A history of haemolytic anaemia or significantly abnormal haematology results at screening.
- History of severe cardiac disease previous six months.
- Impaired renal function
- Patients taking ethinyl estradiol
- Participation in other clinical trials with a new chemical entity within the previous 3 months.
- Inability or unwillingness to comply with the provisions of this protocol
- Females who are lactating or pregnant.
- Males or females (after menarche) not willing to use highly effective contraception (progesterone-only hormonal anticonception with inhibition of ovulation or sexual abstinence) and barrier contraception (condoms), if sexually active during the treatment period and in the following 7 months
- Presence of serious disease or condition, which in the opinion of the investigator makes the patient non-eligible for the study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Active treatment
Pleconaril: 5 mg/kg x2 times a day for 26 weeks up to 40 kg.
Max dose 300mg x2.
Ribavirin:15 (7.5) mg/kg/day divided in two doses daily for 26 weeks: Max dose 1000mg/24h if body weight<75kg and 1200mg if body weight>75kg.
|
Randomized to treatment with study drugs (ribavirin and pleconaril)
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Placebo Comparator: Placebo
Receives placebo, on a double blind basis
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Randomized to treatment with placebo
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Insulin secretion
Time Frame: 12 months
|
Change in mean residual insulin secretion in the Insulin tolerance test (ITT)-population measured by Mixed Meal Tolerance Test (MMTT) stimulated C-peptide two-hour area under the curve profile from visit 1 to12 months after initiation of study treatment.
|
12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Insulin secretion
Time Frame: 3 months
|
Change in mean residual insulin secretion in the ITT-population measured by Mixed Meal Tolerance Test (MMTT) stimulated C-peptide two-hour area under the curve profile from visit 1 to 3 months after initiation of study treatment.
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3 months
|
Insulin secretion
Time Frame: 6 months
|
Change in mean residual insulin secretion in the ITT-population measured by Mixed Meal Tolerance Test (MMTT) stimulated C-peptide two-hour area under the curve profile from visit 1 to 6 months after initiation of study treatment.
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6 months
|
Insulin secretion
Time Frame: 24 months
|
Change in mean residual insulin secretion in the ITT-population measured by Mixed Meal Tolerance Test (MMTT) stimulated C-peptide two-hour area under the curve profile from visit 1 to 24 months after initiation of study treatment.
|
24 months
|
Insulin secretion
Time Frame: 36 months
|
Change in mean residual insulin secretion in the ITT-population measured by Mixed Meal Tolerance Test (MMTT) stimulated C-peptide two-hour area under the curve profile from visit 1 to 36 months after initiation of study treatment.
|
36 months
|
Stimulated c-peptide
Time Frame: 36 months
|
Proportion of patients with peak residual insulin secretion measured by MMTT: stimulated C-peptide >0.2 pmol/L
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36 months
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C-peptide filter paper
Time Frame: 36 months
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Fasting and meal stimulated C-peptide from blood sampled on filter paper at home at 4 weekly intervals throughout the study period
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36 months
|
Insulin dose
Time Frame: 36 months
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Mean Insulin dosage per kilo bodyweight per 24 hours
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36 months
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HbA1c
Time Frame: 36 months
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HbA1c at every control
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36 months
|
Hypoglycemic events
Time Frame: 36 months
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Number of severe hypoglycaemic events and less severe events requiring assistance from others with blood glucose values ≤ 3.9 mmol/L will be registered at each control
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36 months
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Insulin-dose-adjusted HbA1c (IDAA1c)
Time Frame: 36 months
|
HbA1c adjusted to insulin dose
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36 months
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Proinsulin/c-peptide ratio in serum
Time Frame: 36 months
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Proinsulin/c-peptide ratio in serum as a measure of beta cell stress
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36 months
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Presence of enterovirus
Time Frame: 36 months
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Presence of enterovirus and rhinovirus and/or neutralizing antibodies against those viruses in nose, blood, saliva and stool
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36 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Knut Dahl-Jørgensen, MD, PhD, Professor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 30, 2018
Primary Completion (Actual)
October 25, 2020
Study Completion (Actual)
October 25, 2020
Study Registration Dates
First Submitted
January 4, 2019
First Submitted That Met QC Criteria
April 6, 2021
First Posted (Actual)
April 8, 2021
Study Record Updates
Last Update Posted (Actual)
April 8, 2021
Last Update Submitted That Met QC Criteria
April 6, 2021
Last Verified
April 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Immune System Diseases
- Autoimmune Diseases
- Endocrine System Diseases
- Picornaviridae Infections
- Diabetes Mellitus
- Diabetes Mellitus, Type 1
- Enterovirus Infections
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites
- Ribavirin
- Pleconaril
Other Study ID Numbers
- 2015-003350-41
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
IPD Plan Description
The data and material collected from the placebo-group will be shared with the "Innodia" consortium
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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