Repurposing colchicine for reduction of residual inflammatory risk in type 1 diabetes (REC1TE): a randomized, double-blind, placebo-controlled, investigator-initiated trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gentofte Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Diseases [C] - Hormonal diseases [C19], Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

25 Aug 2023 → ongoing

Decision date (initial)

2023-01-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

JDRF

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary aim is to determine the effect of colchicine on levels of high-sensitivity C-reactive protein (mg/l) as compared with placebo following 26 weeks of treatment

Conditions and MedDRA coding

Type 1 diabetes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Type 1 diabetes for more than five years according to World Health Organization criteria
2. Age 18–80 years
3. HbA1c < 80 mmol/mol
4. Stable insulin therapy (defined as no change in insulin brand and not newly initiated continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) therapy) and, if applicable, stable usage of glucose monitoring technology (e.g., continuous glucose monitoring CGM or intermittently scanned CGM) ≥ 3 months with either MDI or CSII
5. C-reactive protein ≥ 2 mg/l (measured by high-sensitivity assay)
6. Estimated glomerular filtration rate > 50 ml/min/l/1.73 m^2
7. Either stable atherosclerotic cardiovascular (CV) disease (as defined by ischaemic heart disease including previous acute myocardial infarction, acute coronary syndrome and coronary revascularization; other arterial revascularization procedures; stroke and transient ischaemic attack; aortic aneurysm; peripheral arterial disease, including carotid atherosclerosis) or high risk thereof ((i.e., high or very high CV risk) as defined by the European Society of Cardiology (Eur Heart J 2020; 41: 255–323) or 10-year CV risk ≥ 20 % (i.e., high CV risk) as according to ‘Steno Type 1 Diabetes Risk Engine’ (https://steno.shinyapps.io/T1RiskEngine/)

Exclusion criteria 22

1. Hypoglycemia unawareness (inability to register low blood glucose) am modum Pedersen-Bjergaard, unless usage of CGM with alarm function
2. Thrombocyte count < 110 X 10^9/L
3. Systemic (oral or intravenous), long-term steroid therapy (topical or inhaled steroids are allowed)
4. Hemodialysis or peritoneal dialysis therapy (since colchicine cannot be removed by dialysis or exchange transfusion)
5. Renal or hepatic impairment treated with a P-gp inhibitor or a strong CYP3A4 inhibitor
6. Other concomitant disease or treatment that according to the investigator's assessment makes the person unsuitable for study participation
7. Alcohol/drug abuse
8. Fertile women not using chemical (tablet/pill, depot injection of progesterone, subdermal gestagen implantation, hormonal vaginal ring or transdermal hormonal patch) or mechanical (spirals) contraceptives
9. Pregnant or nursing women
10. On permanent treatment with colchicine that is not discontinued within 30 days of visit 0
11. Known or suspected hypersensitivity to colchicine
12. Liver disease with elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within seven days , and the last measured value as being conclusive)
13. Receipt of any investigational drug within 30 days prior to visit 0
14. Simultaneous participation in any other clinical intervention trial
15. History of cirrhosis, chronic active hepatitis or severe hepatic disease
16. Inflammatory bowel disease or chronic diarrhea
17. Pre-existing progressive neuromuscular disease or persons with creatinine kinase levels > three times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value as being conclusive)
18. Cancer or lymphoproliferative disease unless in complete remission for > 5 years
19. Immunosuppressive therapy or state of chronic immunodeficiency, including infection with human immunodeficiency virus (HIV)
20. Blood dyscrasias (e.g., myelodysplastic syndromes or related hematological disorders)
21. Leukocyte cell count < 3.0 X 10^9/L
22. Intake of grape fruit juice during trial participation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Estimated treatment difference in high-sensitivity C-reactive protein (mg/l) for colchicine as compared with placebo after 26 weeks of treatment

Secondary endpoints 17

1. High-sensitivity C-reactive protein (mg/l) (measured at week 30)
2. Glycated haemoglobin (mmol/mol; %-point)
3. Time spent in target glycemia (3.9–10 mmol/l) (% of 24 hours) as assessed by continuous glucose monitoring
4. Time spent in hyperglycaemia level 1 (10–13.9 mmol/l) (% of 24 hours) as assessed by continuous glucose monitoring
5. Time spent in hyperglycaemia level 2 (> 13.9 mmol/l) (% of 24 hours) as assessed by continuous glucose monitoring
6. Time spent in hypoglycaemia level 1 (3.0–3.8 mmol/l) (% of 24 hours) as assessed by continuous glucose monitoring
7. Time spent in hypoglycaemia level 2 (< 3.0 mmol/l) (% of 24 hours) as assessed by continuous glucose monitoring
8. Insulin dosage, long-acting (units/day)
9. Insulin dosage, short-acting (units/day)
10. Body weight (kg)
11. Waist:hip ratio
12. Low-density lipoprotein cholesterol (mmol/l)
13. Interleukin-6 (pg/ml)
14. Tumour necrosis factor alpha (pg/ml)
15. Serious adverse events (SAE)
16. Events of severe hypoglycemia
17. Events of diabetic ketoacidosis

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gentofte Hospital

Sponsor organisation

Gentofte Hospital

Address

Kildegårdsvej 28

City

Hellerup

Postcode

2900

Country

Denmark

Scientific contact point

Organisation

Gentofte Hospital

Contact name

Center for Clinical Metabolic Research

Public contact point

Organisation

Gentofte Hospital

Contact name

Center for Clinical Metabolic Research

Third parties 1

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications