NCT06082063

Brief Summary

A prospective, randomised, open-labelled, multi-center study. The aim of the Steno 1 study is to test multifactorial intervention in individuals with type 1 diabetes at high risk of CVD with ambitious treatment targets. We will include 2000 participants. Follow-up is 5 years.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2,000

participants targeted

Target at P50-P75 for phase_3 cardiovascular-diseases

Timeline
38mo left

Started Jul 2024

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress37%
Jul 2024Jul 2029

First Submitted

Initial submission to the registry

May 16, 2023

Completed
5 months until next milestone

First Posted

Study publicly available on registry

October 13, 2023

Completed
9 months until next milestone

Study Start

First participant enrolled

July 1, 2024

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2029

Last Updated

January 10, 2025

Status Verified

January 1, 2025

Enrollment Period

5 years

First QC Date

May 16, 2023

Last Update Submit

January 8, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • MACE + HHF

    Calculate the incidence of cardiovascular events (MACE+HF) to determine whether a multifactorial intervention is superior to standard care with respect to MACE+HHF (composite of time to first non-fatal myocardial infarction, first non-fatal stroke, cardiovascular death or first hospitalization for heart failure).

    5 years

Secondary Outcomes (3)

  • All-cause mortality

    5 years

  • Renal function

    5 years

  • Diabetic ketoacidosis, safety

    5 years

Other Outcomes (18)

  • Indivudual components of the primary endpoint

    5 years

  • Lower extremity amputations

    5 years

  • Progression of retinopathy

    5 years

  • +15 more other outcomes

Study Arms (2)

Multifactorial intervention group

ACTIVE COMPARATOR

The multifactorial intervention will be determined by the risk profile and risk markers of each individual and the participants will be allocated to Semaglutide, sotagliflozin or finerenone. The intervention will also comprise more ambitious treatment targets for blood pressure and lipid levels. In addition, all participants will take aspirin 75 mg OD.

Drug: Aspirin tabletDrug: SemaglutideDrug: SotagliflozinDrug: Finerenone

Standard intervention group

NO INTERVENTION

During the whole study period the standard intervention shall be done according to current Danish and international (ADA/EASD) guidelines. This will address similar risk factors as in the intensive group, but to a less ambitious treatment target for blood pressure and lipid lowering and will not include the use of SGTL2i, finerenone or GLP-1RA, unless these drug classes become recommended in future versions of guidelines.

Interventions

Antiplatelet treatment: with aspirin 75mg OD is mandatory except for concomitant anticoagulant therapy or allergy. In case of allergy clopidogrel will be used.

Multifactorial intervention group

GLP-1RA treatment: With semaglutide once weekly individually stepped highest tolerable dose according to standard guidelines aiming at 1 mg/week for persons with HbA1c \>53 mmol/mol or BMI\>25 kg/m2 and/or ischemic heart disease and/or stroke. For safety see below under benefits and risks. Investigators should pay attention to the need for adjustment in insulin dose after initiation of GLP-1RA treatment.

Multifactorial intervention group

SGLT2i treatment with sotagliflozin 200 mg once daily for persons with UACR \>30 mg/g and eGFR \< 45 ml/min/1.73 m2 and for persons with a diagnosis of HF. For safety see below under benefits and risks. The limit of eGFR (\<45ml/min) for initiation of SGLT2i treatment is set to reduce risk of ketoacidosis. SGLT2i treatment should not be offered to participants on insulin pump therapy, to reduce risk of ketoacidosis. Investigators should pay attention to the need for adjustment in insulin dose after initiation of SGLT2i treatment.

Multifactorial intervention group

Finerenone: 10 mg once daily titrated to 20 mg as add-on in persons with persistent albuminuria (\>30 mg/g) despite RAS blockade.

Multifactorial intervention group

Eligibility Criteria

Age40 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Given written informed consent
  • Male or female patients ≥40 years old with type 1 diabetes (diagnosis before age 30 with insulin from onset or if diagnosis after 30 years of age insulin from onset and DKA or positive autoantibodies ( in accordance with local guidelines)) during \>10 years.
  • Presence of chronic kidney disease (UACR \>30 mg/g or eGFR \< 60 ml/min/1.73 m2) OR history of ischemic heart disease (previous myocardial infarction, stroke or angina) OR history of heart failure OR obesity grade 2 and 3 (BMI\>35 kg/m2) OR 10-year CVD risk \>10% according to Steno Type 1 Risk Engine.
  • Fertile females must use highly efficient chemical, hormonal and mechanical contraceptives during the whole study and at least 2 months after cessation of study drug. The following contraceptive methods are approved: IUD or hormonal contraception that inhibits ovulation, i.e. pills, implantations, transdermal patches, vaginal ring or depot injection. Alternatively, be in menopause (i.e. must not have had regular menstrual bleeding for at least one year), have undergone bilateral oophorectomy or have been surgically sterilized or hysterectomised at least 12 months prior to screening. Fertile participants will be pregnancy tested every six months with urine HCG.
  • Ability to communicate with the investigator and understand informed consent.

You may not qualify if:

  • Type 2 diabetes, MODY, secondary diabetes.
  • History of pancreatitis.
  • Body mass index \< 18.5 kg/m2
  • Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods.
  • Known or suspected abuse of alcohol or recreational drugs.
  • Participant in another intervention study.
  • CKD stage 5.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Rigshospitalet

Copenhagen, Denmark

RECRUITING

Steno Diabetes Center Copenhagen

Herlev, 2730, Denmark

RECRUITING

Related Publications (1)

  • Rossing P. Experimental Designs for Multicomponent Interventions in Kidney and Cardiometabolic Diseases. J Am Soc Nephrol. 2024 Oct 1;35(10):1438-1441. doi: 10.1681/ASN.0000000000000449. Epub 2024 Jul 5. No abstract available.

MeSH Terms

Conditions

Cardiovascular DiseasesHeart FailureDiabetes Mellitus, Type 1Renal Insufficiency

Interventions

Aspirinsemaglutide(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triolfinerenone

Condition Hierarchy (Ancestors)

Heart DiseasesDiabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System DiseasesKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

SalicylatesHydroxybenzoatesPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Study Officials

  • Peter Rossing, MD, DMSc, Proffessor

    Steno Diabetes Center Copenhagen

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Frederik Persson, MD, DMSc

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: This study uses a PROBE design (prospective, cluster-randomized, open, blinded endpoint evaluation). The study is a superiority trial.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 16, 2023

First Posted

October 13, 2023

Study Start

July 1, 2024

Primary Completion (Estimated)

July 1, 2029

Study Completion (Estimated)

July 1, 2029

Last Updated

January 10, 2025

Record last verified: 2025-01

Data Sharing

IPD Sharing
Will not share

Locations