Clinical trial NCT04838145: The Diabetes Virus Detection and Intervention Trial
Official title: The Diabetes Virus Detection and Intervention Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type1 Diabetes Mellitus
Enterovirus
Keywords: Type 1 diabetes
Children
Enterovirus
Recent onset
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
First posted: 2021-04-08
Enrollment: 96
Sex: ALL
Minimum age (years): 6
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A double-blind, placebo controlled, prospective, randomized trial examining the effect of antiviral treatment given for 6months on residual insulin secretion
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

1. Diagnosed type 1 Diabetes (E10.9). First injection of insulin maximum three weeks prior to inclusion.
2. Must be willing and capable of taking the study drugs and meet for tests and follow up as described.
3. 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.
4. Aged 6.00-15.99 years at inclusion

Exclusion Criteria:

1. Treatment with any oral or injected anti-diabetic medications other than insulin.
2. A history of haemolytic anaemia or significantly abnormal haematology results at screening.
3. History of severe cardiac disease previous six months.
4. Impaired renal function
5. Patients taking ethinyl estradiol
6. Participation in other clinical trials with a new chemical entity within the previous 3 months.
7. Inability or unwillingness to comply with the provisions of this protocol
8. Females who are lactating or pregnant.
9. 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
10. Presence of serious disease or condition, which in the opinion of the investigator makes the patient non-eligible for the study.

Primary outcomes:
measure: Insulin secretion
timeFrame: 12 months
Secondary outcomes:
measure: Insulin secretion
timeFrame: 3 months
measure: Insulin secretion
timeFrame: 6 months
measure: Insulin secretion
timeFrame: 24 months
measure: Insulin secretion
timeFrame: 36 months
measure: Stimulated c-peptide
timeFrame: 36 months
measure: C-peptide filter paper
timeFrame: 36 months
measure: Insulin dose
timeFrame: 36 months
measure: HbA1c
timeFrame: 36 months
measure: Hypoglycemic events
timeFrame: 36 months
measure: Insulin-dose-adjusted HbA1c (IDAA1c)
timeFrame: 36 months
measure: Proinsulin/c-peptide ratio in serum
timeFrame: 36 months
measure: Presence of enterovirus
timeFrame: 36 months
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Pediatric department, Oslo University Hospital
Study officials:
affiliation: Professor
name: Knut Dahl-Jørgensen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: