The ADDITION Study. Intensive Treatment in People With Screen Detected Diabetes in Primary Care. (ADDTION)

December 19, 2013 updated by: University of Aarhus

The ADDITION Study. Anglo-Danish-Dutch Study of Intensive Treatment In PeOple With screeN Detected Diabetes in Primary Care

The ADDITION study comprise 2 parts: screening for Type 2 diabetes and intensive treatment compared to standard treatment.

  1. In the screening study, the feasibility and results of country specific models to identify undiagnosed individuals with Type 2 diabetes will be evaluated.
  2. In the treatment study the effects of routine care in general practice according to local and national guidelines will be compared with an intensive ADDITION protocol, including structured lifestyle education (dietary modification, increased physical activity and smoking cessation) and intensive treatment of blood glucose, blood pressure and lipids, and prophylactic aspirin with or without motivational interviewing, on mortality, macrovascular and microvascular disease. Furthermore the impact of treatment on health status, treatment satisfaction and health service costs will also be assessed.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Aims:

  • To develop and evaluate strategies for early detection of type 2 diabetes in different countries and different populations.
  • To study whether a multifactorial treatment strategy can reduce CVD-mortality and reduce the incidence of macro- and microvascular complications. The treatment strategy consists of motivational interviewing, encouraging behavioural changes (dietary advises, physical activity, smoking cessation) and intensive pharmacological treatment of blood pressure, blood glucose, and serum lipids
  • To identify genetic markers predicting development of diabetic complications
  • To evaluate health economical consequences of screening and early intervention for type 2 diabetes

Design and methods:

The study is an investigator initiated and designed study, initiated in Denmark by the two principal investigators, planned and conducted in collaboration between the four centers in Denmark, UK and the Netherlands. The study has two elements: a screening study and a subsequent intervention study.

In the screening study, the feasibility and results of country specific models to identify undiagnosed individuals with Type 2 diabetes will be evaluated.

In the treatment study the effects of routine care in general practice according to local and national guidelines will be compared with an intensive ADDITION protocol, including structured lifestyle education (dietary modification, increased physical activity and smoking cessation) and intensive treatment of blood glucose, blood pressure and lipids, and prophylactic aspirin with or without motivational interviewing, on mortality, macrovascular and microvascular disease. Furthermore the impact of treatment on health status, treatment satisfaction and health service costs will also be assessed.

Methodology - Screening study:

In Denmark > 300 primary care physicians from 5 different counties (Copenhagen, Aarhus, Ringkøbing, Ribe and Sønderjylland) participate in the study. Diabetes-related information is sent to all individuals aged 40-69 years enrolled in their practice. A questionnaire (diabetes risk score29) including age, gender, family history of type 2 diabetes; obesity; physical activity and previously diagnosed hypertension was used. Individuals scoring high on the questionnaire are encouraged to contact their physician for an examination of random blood glucose (RGB) and HbA1c. A step-wise strategy based on RBG, HbA1c, FPG and OGTT is used to diagnose diabetes In the Netherlands all people aged 50-69 years and listed with the participating primary care physicians is invited to fill in a diabetes risk questionnaire based on the same risk factors as in Denmark. Those at high risk of having type 2 diabetes are requested to come for a screening visit at a centre set up near the general practice. A stepwise screening strategy based on RBG, FPG and OGTT is used to diagnose diabetes In UK, different strategies are used in Cambridgeshire and Leicester. In Cambridgeshire a search of computerised general practice records is performed, using a simple validated risk score, based on routine general practice data (age, gender, prescribed medication and body mass index), to identify people in the age of 40-69 years at high risk of having undiagnosed diabetes30. Those with a high score undergo a stepwise screening strategy based on RBG, FPG and OGTT is used to diagnose diabetes In Leicester all white European subjects aged 40-75 years and Asian, black or Chinese subjects aged 25-75 years are invited in a restricted geographical region within Leicester. All attendant undergo an OGTT as the first screening step (unless FPG > 7.0 mmol/l)

Diagnostic procedures:

The diagnostic procedure includes a stepwise procedure minimizing the work-load on the general practitioner and includes the questionnaire, random capillary blood glucose and HbA1c as screening instruments followed by fasting capillary blood glucose (FCBG) and an oral glucose tolerance test in everyone with marginally elevated FCBG. The diagnostic criteria follow the most recent World Health Organization guidelines (31) and are based on two diagnostic glucose values measured on independent days.

Exclusion criteria:

Participants are excluded if they already have diabetes, are pregnant or lactating or have a severe psychotic illness, are house bound or have an illness with a likely survival of less than one year.

Outcome measures:

Outcome measures from the screening study include measures of the efficacy of the screening campaign, the objective health status of patients newly identified by the campaign, feasibility as reported by the primary care physician, and the economic impact or benefit of the a programme. Furthermore a substudy explores the psycho-social and ethical aspects of the screening programme.

Methodology - Intervention study:

All patients diagnosed as part of the screening programme are invited to enter the ADDITION-study. The study will include a minimum of 3000 patients with screen detected diabetes. The general practices are randomised to the routine care group (standard care as given by the GP) or to the intervention group which features a target driven, intensive multifactorial approach to treatment. The study is an open, multicentre, parallel group trial with randomisation of general practices. Patients are screened and recruited during the period January 1st 2000 and June 30th 2006. The end of follow up is by July 1st 2009. Participation is based on informed consent in accordance with the Declaration of Helsinki.

Intensive Treatment strategy:

The intensive multifactorial treatment includes lifestyle advices (concerning diet, physical activity, medication adherence and tobacco cessation), prescription of aspirin and stepwise increases in pharmacological treatment of blood glucose, blood pressure and lipids, according to strict targets (appendix 1). The treatment targets are as follows:

  • HbA1c < 7.0
  • Total cholesterol < 5.0 mmol/l (4.5 mmol/l if CVD present)but statin to everyone with total cholesterol > 3.5 mmol/l
  • Blood pressure < 135/85
  • Aspirin 75- 150 mg/day to everyone on antihypertensive treatment Behavioural advices include
  • Smoking cessation
  • Physical activity 30 min./day
  • Healthy diet (low fat, 600g of fruit and vegetables/day)

The treatment targets may be intensified during the study according to the results of other clinical trials published during the study period, as the aim is to strive for treatment targets based on the most intensive guidelines available.

Within the intensive group a further randomisation allocates 50% of the patients to country specific interventions concerned with improving adherence to lifestyle changes and medication. This intervention, including the use of motivational interviewing) is delivered either by a trained facilitator (UK and The Netherlands) or through training of practitioners (Denmark), and is based on a client-centred non-directive counseling style to help patients explore and resolve ambivalence and stimulate lifestyle changes, appropriate diabetes self-care and adherence to medical treatment 32,33.

Pharmacological treatment:

The decision on which pharmaceutical drug to use for the individual patients with is made by the clinician as the study is target driven and not a trial comparing different specific drugs. The clinician is provided with recommendations for a treatment strategy (appendix 1), which should be based on balancing treatment effect, side-effects and cost. The main priority is achievement of treatment targets with a flexible lifestyle and low rates of side effects such as hypoglycaemia and weight gain.

Therapies are adjusted at 2 to 4-weekly intervals until targets are reached, thereafter every 3 months. HbA1c is taken every third month, in between antidiabetic drugs are adjusted according to blood glucose measurements in the interim.

Outcome measures: see other section.

Sample size and statistical power:

Based on levels of risk in the conservative-treatment arm of the UKPDS, the expected event rate is 3% per year for the combined endpoint (all-cause mortality, nonfatal myocardial infarction, stroke, revascularisation or amputation). With a sample size of 1350 patients in each arm (standard versus intensive treatment) the study will allow the detection of a 30% risk reduction in the intervention group at a significance level of 5% with a mean duration of follow-up of 5 years.

Timescale:

The screening study began in late 2000 and will end by June 30th 2006. Patients are enrolled into the treatment study following diagnosis in the screening study: thus the treatment study proceeds along with the evaluation phase of the screening study. The follow-up will continue until July 1st 2009.

Ethics and safety:

The Scientific Ethics Committee in the involved counties in Denmark and the Multipractice Study Committee have accepted the project, and the study has been approved by the ethical committees in UK and the Netherlands.

A data safety and monitoring committee will have access to all end point data (unblinded) after 1, 3 and 5 years, and the study will be terminated if the composite end point (including: Cardiovascular death, non-fatal MI, non-fatal stroke, revascularisation and amputation) should demonstrate a clear advantage of intensive versus standard treatment (p<0.001) or a clear advantage of the standard versus intensive treatment (p<0.01).

Perspectives of the trial:

The results of the study will be of immediate national and international relevance to policy decisions about screening for diabetes, and subsequent intensive treatment. If the study shows that screening and early intervention markedly reduces the risk of developing premature CVD, then the study will have potential important impact at the individual patient level as well as on the societal level. If the study fails to show an effect of screening and early intensive treatment then this would have direct impact on future recommendations for screening and treatment regimens, and the study could lead to significant savings if it shows that strict treatment targets are not essential in the early phase of the disease. The results of the sub-study will inform approaches to health promotion to the management of chronic disease and risk, and to strategies to support adherence applicable not only to diabetes but also to other chronic diseases.

References and Appendix 1 on www.addition.au.dk

Study Type

Interventional

Enrollment (Actual)

3057

Phase

  • Not Applicable

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

  • Denmark
      • Aarhus, Denmark, 8000
        • Institute of Public Health
  • Netherlands
      • Utrecht, Netherlands
        • Julius Centre for health Sciences and Primary Care, University of Utrecht
  • United Kingdom
      • Cambridge, United Kingdom, UK CB2 2SR
        • Department of Public Health and General Practice
      • Leicester, United Kingdom
        • University Hospital and Department of Health Sciences, University of Leicster

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

40 years to 69 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Screening study: Every one aged 40-69 years (UK and DK) or 50-69 years(NL). Treatment study: All with screen detected type 2 diabetes.

Exclusion Criteria:

Participants are excluded if they already have diabetes at time of screening, are pregnant or lactating or have a severe psychotic illness, are house bound or have an illness with a likely survival of less than one year.

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention
The 334 general practices in Denmark, United Kingdom and the Netherlands have been randomised to screening for diabetes followed by routine care (RC group) according to national guidelines, or screening followed by multifactorial treatment (IT group).
Procedure: optimised treatment

The intervention targeted individual patients and the Primary Care Team. Practitioners were trained in a target driven, intensive multifactorial approach including lifestyle advice (smoking cessation, physical activity 30 min./day and healthy diet) and pharmacological treatment with the aim of reducing the complications of diabetes as described in protocol.

The training included meetings, practice visiting, written feed back reports and reminders on controls.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Cardiovascular mortality
Time Frame: Sept 2010
Sept 2010
MI (non fatal)
Time Frame: Sept 2010
Sept 2010
Stroke (non fatal)
Time Frame: Sept 2010
Sept 2010
Revascularisation (operating procedures)
Time Frame: Sept 2010
Sept 2010
Amputations, non traumatic
Time Frame: Sept 2010
Sept 2010

Secondary Outcome Measures

Outcome Measure
Time Frame
All cause mortality
Time Frame: 2010
2010
Development of renal impairment
Time Frame: 2010
2010
Progression of retinopathy
Time Frame: 2010
2010
Health economy, patient and health service costs and gains
Time Frame: 2010
2010
Perceived health, SF36, AddQol
Time Frame: 2010
2010
Neuropathy, periphery and autonomy
Time Frame: 2011
2011

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Collaborators

University Hospitals, Leicester
University of Cambridge
Utrecht University
Steno Diabetes Centre, Gentofte, Denmark

Investigators

  • Study Chair: Torsten Lauritzen, Professor, Institutute of Public Health, Dep. of General practice, Aarhus University, Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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

January 1, 2001

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

October 10, 2005

First Submitted That Met QC Criteria

October 10, 2005

First Posted (Estimate)

October 12, 2005

Study Record Updates

Last Update Posted (Estimate)

December 20, 2013

Last Update Submitted That Met QC Criteria

December 19, 2013

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • The ADDITION-study

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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