Diabetes Research on Patient Stratification (DIRECT)

• ClinicalTrials.gov Identifier: NCT03814915
• Recruitment Status: Completed
• First Posted: January 24, 2019
• Last Update Posted: January 18, 2020
• Sponsor: Lund University
• Information provided by (Responsible Party): Lund University

Study Description

Brief Summary:

The overarching goal of the IMI DIRECT (Innovative Medicines Initiative Diabetes Research on Patient Stratification) Consortium is the identification of biomarkers that aid therapeutic targeting in prediabetes (Study 1) or early onset type 2 diabetes (Study 2).

Condition or disease
Type2 Diabetes

Detailed Description:

There are two multicentre prospective cohort studies within the glycaemic deterioration work package of IMI DIRECT (WP2). These two cohorts are designed to address the area of glycaemic deterioration by amassing data and biomaterials that will be used to discover novel biomarkers for glycaemic deterioration in people at high risk of developing type 2 diabetes (Study 1) and in those who have recently been diagnosed with the disease (Study 2).

Study Design

• Study Type: Observational
• Actual Enrollment: 3049 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: DIabetes REsearCh on Patient straTification
• Actual Study Start Date: October 15, 2012
• Actual Primary Completion Date: July 31, 2019
• Actual Study Completion Date: July 31, 2019

Groups and Cohorts

Group/Cohort
Study 1 - Prediabetes; The primary objective of Study 1 is to collect biosamples and information that might yield novel, predictive biomarkers for glycaemic deterioration in non-diabetic high-risk participants. Participants in Study 1 were recruited from existing prospective cohort studies in or around each of the following European cities: Malmö, Sweden (Malmö Diet and Cancer Study); Amsterdam, The Netherlands (Hoorn Study); Copenhagen, Denmark (Inter99); and Kuopio, Finland (METSIM). A clinically practicable screening tool (DIRECT-DETECT) was used to identify at-risk participants from existing cohort studies, who were then recruited into this new prospective cohort study (Study 1).
Study 2- Diabetic; The primary objective of Study 2 is to collect biosamples and information that might yield novel, predictive biomarkers for glycaemic deterioration in people who have recently been diagnosed with type 2 diabetes. Participants in Study 2 of DIRECT are recruited from or nearby each of the following European cities: Malmö, Sweden; Amsterdam, the Netherlands; Copenhagen, Denmark; Exeter, UK; Newcastle, UK; Dundee, UK. Potential participants are recruited through targeted searches of existing databases and research registers combined with person-to-person contact at educational clinics and through routine retinal screening programmes.

Outcome Measures

Primary Outcome Measures :

1. Glycemic deterioration [ Time Frame: Up to 10 years follow-up ]
   Change in glucose (or HbA1c) over time and/or progression to anti diabetic medications/insulin

Biospecimen Retention:   Samples With DNA

Blood Omics: Fasting blood samples taken for genomic, transcriptomic, proteomic and metabolomic assessments.

Microbiome Urine Toenail clippings

Eligibility Criteria

• Ages Eligible for Study: 35 Years to 74 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

White European (self-report of parental ethnicity), Age ≥35 and <75 years

Criteria

Study 1

Inclusion criteria

• No treatment with insulin-sensitising, glucose-lowering or other antidiabetic drugs
• Fasting capillary blood glucose <10 mmol/l at baseline
• White European (self-report of parental ethnicity)
• Age ≥35 and <75 years

Exclusion criteria

• Diagnosed diabetes of any type, HbA1c ≥6.5% (48 mmol/mol) or fasting plasma glucose ≥7.0 mmol/l or 2 h plasma glucose >11.0 mmol/l previously
• For women, pregnancy, lactation or plans to conceive within the study period
• Use of a pacemaker
• Any other significant medical reason for exclusion as determined by the investigator

Study 2

Inclusion Criteria:

• Patients diagnosed with type 2 diabetes not less than 6 months and not more than 24 months before baseline examination
• Management by lifestyle with or without metformin therapy
• All HbA1c <7.6% (<60 mmol/mol) within previous 3 months
• White European
• Age ≥35 and <75
• Estimated GFR >50 ml/min'

Exclusion Criteria:

• Type 1 diabetes

  • A previous HbA1c >9.0% (>75 mmol/mol)
  • Prior treatment with insulin or an oral hypoglycaemic agent other than metformin
  • BMI <20 or >50 kg/m2
  • Pregnancy, lactation or plans to conceive within the study period
  • Any other significant medical reason for exclusion as determined by the investigator

Contacts and Locations

Sponsors and Collaborators

Lund University

Investigators

• Principal Investigator: Ewan Pearson, FRCP; University of Dundee
• Principal Investigator: Paul W Franks, PhD; Lund University

More Information

Publications:

Koivula RW, Heggie A, Barnett A, Cederberg H, Hansen TH, Koopman AD, Ridderstråle M, Rutters F, Vestergaard H, Gupta R, Herrgård S, Heymans MW, Perry MH, Rauh S, Siloaho M, Teare HJ, Thorand B, Bell J, Brunak S, Frost G, Jablonka B, Mari A, McDonald TJ, Dekker JM, Hansen T, Hattersley A, Laakso M, Pedersen O, Koivisto V, Ruetten H, Walker M, Pearson E, Franks PW; DIRECT Consortium. Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: rationale and design of the epidemiological studies within the IMI DIRECT Consortium. Diabetologia. 2014 Jun;57(6):1132-42. doi: 10.1007/s00125-014-3216-x. Epub 2014 Apr 4.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Atabaki-Pasdar N, Ohlsson M, Viñuela A, Frau F, Pomares-Millan H, Haid M, Jones AG, Thomas EL, Koivula RW, Kurbasic A, Mutie PM, Fitipaldi H, Fernandez J, Dawed AY, Giordano GN, Forgie IM, McDonald TJ, Rutters F, Cederberg H, Chabanova E, Dale M, Masi F, Thomas CE, Allin KH, Hansen TH, Heggie A, Hong MG, Elders PJM, Kennedy G, Kokkola T, Pedersen HK, Mahajan A, McEvoy D, Pattou F, Raverdy V, Häussler RS, Sharma S, Thomsen HS, Vangipurapu J, Vestergaard H, 't Hart LM, Adamski J, Musholt PB, Brage S, Brunak S, Dermitzakis E, Frost G, Hansen T, Laakso M, Pedersen O, Ridderstråle M, Ruetten H, Hattersley AT, Walker M, Beulens JWJ, Mari A, Schwenk JM, Gupta R, McCarthy MI, Pearson ER, Bell JD, Pavo I, Franks PW. Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts. PLoS Med. 2020 Jun 19;17(6):e1003149. doi: 10.1371/journal.pmed.1003149. eCollection 2020 Jun.

• Responsible Party: Lund University
• ClinicalTrials.gov Identifier: NCT03814915
• Other Study ID Numbers: IMIDIRECT_2012
• First Posted: January 24, 2019
• Last Update Posted: January 18, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lund University:

Gene-environment interaction; Genome; Glycaemic control; Lifestyle; Microbiome; Prediabetes; Proteome; Type 2 diabetes

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases