Effect of Diet and Physical Activity on Incidence of Type 2 Diabetes (PREVIEW)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Copenhagen
Sponsor:
Collaborators:
Helsinki University
Maastricht University
University of Nottingham
University of Navarra
Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria
University of Sydney
University of Auckland, New Zealand
University of Stuttgart
Swansea University
Cambridge Manufacturing Company Limited
European Union
Information provided by (Responsible Party):
Anne Birgitte Raben, University of Copenhagen
ClinicalTrials.gov Identifier:
NCT01777893
First received: January 24, 2013
Last updated: January 27, 2014
Last verified: January 2014

January 24, 2013
January 27, 2014
June 2013
December 2017   (final data collection date for primary outcome measure)
Incidence of type 2 diabetes [ Time Frame: 3 years ] [ Designated as safety issue: No ]

For adults:

Incidence of type 2 diabetes, in high protein versus medium protein diet, measured during 3 years after baseline and based on WHO/IDF criteria:

Fasting plasma glucose (FPG) > 7.0 mmol/l (126 mg/dl) or, 75 g oral glucose tolerance test (OGTT) with FPG > 7.0 mmol/l (126 mg/dl) and/or 2 hour plasma glucose > 11.1 mmol/l (200 mg/dl) or, Glycated haemoglobin (HbA1c) > 6.5% (48 mmol/mol), or Random plasma glucose > 11.1 mmol/l (200 mg/dl) in the presence of classical diabetes symptoms.

For children and adolescents:

Change in insulin resistance at 3 years after randomization to high protein versus medium protein diet, measured by insulin resistance analysed by the homeostatic model (HOMA-IR).

Incidence of type 2 diabetes [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Incidence of type 2 diabetes after randomization on high protein versus medium protein diet based on IDF criteria:

Fasting plasma glucose >=7.0 mmol/l or 75 g oral glucose tolerance test with FPG >= 7.0 mmol/l and/or 2hour plasma glucose >=11.1 mmol/l or HbA1c >=6.5% or random plasma glucose >=11.1 mmol/l in the presence of classical diabetes symptoms

for children: Change in glucose tolerance measured by HOMA-IR

Complete list of historical versions of study NCT01777893 on ClinicalTrials.gov Archive Site
  • Incidence of type-2 diabetes [ Time Frame: 3 years ] [ Designated as safety issue: No ]

    For adults:

    The effect of high intensity vs. moderate intensity physical activity on incidence of type 2 diabetes, based on WHO/IDF criteria (adjusted for diet).

    Fasting plasma glucose (FPG) > 7.0 mmol/l (126 mg/dl) or, 75 g oral glucose tolerance test (OGTT) with FPG > 7.0 mmol/l (126 mg/dl) and/or 2 hour plasma glucose > 11.1 mmol/l (200 mg/dl) or, Glycated hemoglobin (HbA1c) > 6.5% (48 mmol/mol), or Random plasma glucose > 11.1 mmol/l (200 mg/dl) in the presence of classical diabetes symptoms.

    For children and adolescents:

    Change in insulin resistance at 3 years after randomization to high intensity vs. moderate intensity physical activity, analyzed by the homeostatic model (HOMA-IR).

  • Change in HbA1c, a measure of average blood glucose levels [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Change in body weight and waist, hip and thigh circumference [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Change in body fat mass (kg, proportion of body weight) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Proportion of subjects maintaining at least 0, 5 or 10% weight loss (relative to initial body weight) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Insulin sensitivity [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Risk factors for cardiovascular disease, with at least the following measures: blood pressure, lipids (triglycerides, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol), C-reactive protein, and liver enzymes [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Changes in perceived quality of life and workability, habitual well-being, sleep and chronic stress, subjective appetite sensations, and habitual physical activity. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • change in body fat mass [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    change in body fat mass assessed with BodPod.
  • sleeping pattern changes due to intervention [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    it is hypothesized that a high-protein, low GI diet in interaction with physical activity may improve the sleeping pattern and reduce levels of chronic stress during the weight maintenance phase
  • changes in brain reward activity [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    it is hypothesized that brain reward activity in response to food cues will decrease in parallel with weight loss.
Not Provided
Not Provided
 
Effect of Diet and Physical Activity on Incidence of Type 2 Diabetes
PREVention of Diabetes Through Lifestyle Intervention and Population Studies in Europe and Around the World

Type-2 diabetes is one of the fastest growing chronic diseases worldwide. This trend is mainly driven by a global increase in the prevalence of obesity. The PREVIEW study has been initialized to find the most effective lifestyle-components (diet and physical activity) to prevent Type-2 diabetes. The project consists of a randomized lifestyle-intervention with the more specific aim to determine the preventative impact of a high-protein and low-GI diet in combination with moderate or high intensity physical activity compared with a moderate-protein and moderate GI diet in combination with the same activity levels on the incidence of Type-2 diabetes in predisposed, pre-diabetic children, young and older adults.

The trial will be performed in 6 EU countries (Bulgaria, Denmark, Finland, Spain, Netherlands, UK) and Australia and New Zealand.

A total of 2,500 overweight or obese participants (200 children and adolescents aged 10—18 y, 800 younger adults, aged 25—45 y, and 1,500 older adults, aged 55—70 y) will be recruited. All adult participants are first treated by a low-calorie diet for 8 weeks, with an aim to reach ≥ 8% weight reduction. Children and adolescents are treated separately with a conventional weight-reduction diet, with-out a specific aim for absolute weight loss.

Before the weight reduction, the participants are randomized into two different diet interventions and two exercise interventions for a total of 148 weeks. This period aims at preventing Type-2 diabetes by weight-maintenance (prevention of relapse in reduced body weight) and by independent metabolic effects of diet and physical activity.

The primary endpoint of the study is the incidence of Type-2 diabetes in the adults during 3 years (156 weeks) according to diet (high protein/low-GI versus moderate protein/moderate-GI, adjusted for physical activity), based on a 75 g oral glucose tolerance test and/or HbA1c. For children and adolescents:

Change in insulin resistance at 3 years after randomization to high protein versus moderate protein diet, measured by insulin resistance analyzed by the homeostatic model (HOMA-IR) as well as physiological improvement of health with respect to pre-diabetic characteristics.

Our hypothesis is that a high-protein, low-GI diet will be superior in preventing type-2 diabetes, compared with a moderate protein, moderate GI diet, and that high-intensity physical activity will be superior compared to moderate-intensity physical activity.

Type-2 diabetes is one of the fastest growing chronic diseases worldwide. This trend is mainly driven by a global increase in the prevalence of obesity. The PREVIEW study has been initialized to find the most effective lifestyle-components (diet and physical activity) in the prevention of T2D. The project is a randomized lifestyle-intervention. The main aim is to determine the preventative impact of a high-protein and low-GI diet in combination with moderate or high intensity physical activity on the incidence of T2D in predisposed, pre-diabetic children, younger and older adults (both gender). In substudies following will be assessed; changes in fat distribution (adults), risk of colon cancer by biomarkers (fecal samples in adults), change in physical fitness (VO2 max in adults), metabolomics profile (adults), food reward (children and adolescents) and sleep architecture (children and adolescents).

Objective: The project addresses prevention in individuals with high risk for T2D. The trial will be performed in 6 EU countries (Bulgaria, Denmark, Finland, Spain, Netherlands, UK), as well as in Australia and New Zealand.

Study design: The PREVIEW intervention study will be carried out as a 3-year randomized, clinical intervention consisting of an initial 8-week weight loss period and a 148 week randomized weight maintenance intervention.

Study population: A total of 2500 participants will participate in the intervention. All adult participants are first treated by a low-calorie diet for 8 weeks, with an aim to reach >8% weight reduction. In skeletal immature children weight loss is not desirable and the goal is to maintain weight (while gaining length) during the initial 8 weeks.

Intervention: The two diet interventions for participants are:

HP = high-protein: protein 25 E%, carbohydrates 45 E%, dietary glycaemic index (GI) <55.

MP = moderate-protein: protein intake 15% in total energy intake (E%), carbohydrates 55 E%, GI >65;

Both diets are composed by using healthy food items.

The two exercise interventions are:

MI = moderate-intensity: 60—75% of maximal heart rate (HRmax), e.g., brisk walking;

HI = high intensity: 76—90% HRmax, e.g., running.

The randomization for the adults is stratified by sex and age group, and by sex in children.

The participants are supervised in groups during the LCD (3—4 times) and throughout the weight-maintenance period. Children are being supervised separately. Meeting frequency is reduced towards the end of the study. The main assessment points (clinical investigation days, CID) are at week 0 (start of weight reduction), week 8 (end of weight reduction/start of randomized intervention), week 26 (6 months from baseline), week 52 (12 months from baseline), week 78 (18 months from baseline) week 104 (24 months from baseline) and week 156 (36 months from baseline / End of Trial, EOT).

Main study endpoints: The primary endpoint of the intervention study is the incidence of Type-2 diabetes during 156 weeks according to diet (high protein versus moderate protein, adjusted for physical activity), based on a 75 g oral glucose tolerance test (OGTT). The incidence of diabetes will be assessed annually by participant self-report of medication requiring diabetes, doctor informed (and confirmed) diabetes diagnosis or diabetes diagnosed by fasting plasma glucose (FPG) and/or OGTT according to IDF guidelines.

For children and adolescents: Change in insulin resistance at 3 years after randomization to high protein versus medium protein diet, measured by insulin resistance analyzed by the homeostatic model (HOMA-IR) as well as physiological improvement of health with respect to pre-diabetic characteristics.

Secondary endpoints are (tested against the four possible combinations of diet and physical activity if not stated otherwise) the effects of high intensity vs. moderate intensity physical activity on incidence of type 2 diabetes, based on WHO/IDF criteria (adjusted for diet); change in HbA1c, a measure of average blood glucose levels; change in body weight and waist, hip and thigh circumference; change in body fat mass (kg, proportion of body weight); proportion of subjects maintaining at least 0, 5 or 10% weight loss (relative to initial body weight); insulin sensitivity (e.g. Matsuda Index based on the OGTT, glucose and insulin area under the curve (AUC) during OGTT, beta-cell disposition index)(only adults); risk factors for cardiovascular disease, with at least the following measures: blood pressure, lipids (triglycerides, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol), C-reactive protein, and liver enzymes; changes in perceived quality of life and workability, habitual well-being, sleep and chronic stress, subjective appetite sensations, and habitual physical activity.

Substudies. Fat distribution: Assessment of fat distribution by MRI (Magnetic Resonance Imaging) and HMRS (Hydrogen Magnetic Resonance Spectroscopy) is done in a sub-group of subjects at University of Maastricht: 20 from HPMI and 20 from MPMI group. MRI and MRS are non-invasive and non-irradiant imaging techniques, which will be used to determine abdominal fat and muscle mass of the upper part of the lower limbs (MRI), muscle and liver fat (HMRS). MRI and MRS measurements take place at weeks 0, 26 and 104.

Sampling and analyses of DNA and RNA: The intended use of the samples is epi/genetic analyses in relation to obesity and associated diseases. Genetic sampling will take place at week 0, 52 and 156.

Metabolomics profile: In a sub-group of subjects, urine from baseline week 0 and week 52 will be analyzed for metabolomics profile.

Fecal samples: Full fecal samples from 3 consecutive days are collected from a sub-group. The samples are used for assessment of colon cancer risk markers, ie phenolic metabolites, short-chain fatty acids (SCFA), nitrogenous compounds. Subjects are recruited from all four groups on a consecutive invitation basis. Moreover, samples from the same subjects are stored for potential analysis of microbiota changes. Fecal samples will be collected during weeks 0, 52 and 156.

Sleep architecture: In a sub-study we will identify the mediating role of sleeping patterns (sleep quality and duration), stress and brain plasticity on the protein/ activity intervention and the outcome parameters. The sub-study assessing the role of sleep and brain plasticity will be conducted as a repeated measures design embedded in the main intervention study. Measurements will be taken at 0, 26 and 104 weeks.

Food reward: A possible relationship of peripheral insulin sensitivity and brain reward activation will be assessed in a sub-group of pre-diabetic adults, consisting of 2 stratified intervention groups. The sub-study will take place in University of Maastricht and will use functional magnetic resonance imaging (fMRI) in a block design with high calorie/ low calorie food images and control images. Measurements of food reward will be done at weeks 0, 8, and 104.

Cost-effectiveness: The adult participants will also fill in a short questionnaire on medicine use, days absent from work, "less than optimal" workability etc. These answers are used to estimate cost-effectiveness of the life-style programs in PREVIEW. Cost-effectiveness will be assessed in week 0, 52, 104, 156.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
  • Pre-diabetes
  • Obesity
  • Behavioral: High protein/ high intensity physical activity (HP-HI)
    Participants follow a high protein diet and a high intensity physical activity intervention
  • Behavioral: High protein / moderate intensity physical activity (HP-MI)
    Participants follow a high protein diet and moderate intensity physical activity intervention
  • Behavioral: Moderate protein/ high intensity physical activity (MP-HI)
    Participants follow a moderate protein diet and a high intensity physical activity intervention
  • Behavioral: Moderate protein/ moderate intensity physical activity (MP-MI)
    Participants follow a moderate protein diet and moderate intensity physical activity intervention
  • Active Comparator: HP-HI
    High protein/ high intensity physical activity
    Intervention: Behavioral: High protein/ high intensity physical activity (HP-HI)
  • Active Comparator: HP-MI
    High protein/ moderate intensity physical activity
    Intervention: Behavioral: High protein / moderate intensity physical activity (HP-MI)
  • Active Comparator: MP-HI
    Moderate protein/ high intensity physical activity
    Intervention: Behavioral: Moderate protein/ high intensity physical activity (MP-HI)
  • Active Comparator: MP-MI
    Moderate protein/ moderate intensity physical activity
    Intervention: Behavioral: Moderate protein/ moderate intensity physical activity (MP-MI)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
2500
December 2017
December 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

For adults:

  1. Age 25 - 45 years and 55 - 70 years
  2. Overweight or obesity status BMI>25 kg/m2
  3. Pre-diabetes The criteria from WHO/IDF (International Diabetes Foundation) for assessing pre-diabetes will be used as the formal inclusion criteria, i.e. having:

    Impaired Fasting Glucose (IFG): Fasting venous plasma glucose concentration 5.6 - 6.9 mmol/l or Impaired Glucose Tolerance (IGT): Venous Plasma glucose concentration of 7.8 - 11.0 mmol/l at 2 h after oral administration of 75 g glucose (oral glucose tolerance test, OGTT), with fasting plasma glucose less than 7.0 mmol/l.

    Due to potential between-lab variation (local assessments), HbA1c is not used as an inclusion criteria in the screening.

  4. Informed consent required
  5. Ethnic group - No restrictions
  6. Smoking - Smoking is allowed, provided subjects have not recently (within 1 month) changed habits. However, smoking status is monitored throughout the study and used as a confounding variable.
  7. Motivation - Motivation and willingness to be randomized to any of the groups and to do his/hers best to follow the given protocol
  8. Other - Able to participate at CID's during normal working hours.

For children and adolescents:

  1. Age 10-18 years
  2. Age-adjusted value corresponding to BMI>25 kg/m2 (Cole et al. 2000)
  3. Since the prevalence of pre-diabetes among children with overweight or obesity is low, it is not feasible to include exclusively pre-diabetic children (according to criteria of the IDF).

    Therefore insulin resistant over-weight/obese children will be included, defined as: HOMA-IR >2

  4. Informed consent required
  5. Ethnic group - No restrictions
  6. Smoking - Smoking is allowed, provided subjects have not recently (within 1 month) changed habits. However, smoking status is monitored throughout the study and used as a confounding variable.
  7. Motivation - Motivation and willingness to be randomized to any of the groups and to do his/hers best to follow the given protocol
  8. Other - Able to participate at CID's during normal school/working hours.

Exclusion Criteria:

Based on interview and/or questionnaire, individuals with the following problems will be excluded:

Medical conditions as known by the subjects:

  1. Diabetes mellitus (other than gestational diabetes mellitus);
  2. Significant cardiovascular disease including current angina; myocardial infarction or stroke within the past 6 months; heart failure; symptomatic peripheral vascular disease ;
  3. Systolic blood pressure above 160 mmHg and/or diastolic blood pressure above 100 mmHg whether on or off treatment for hypertension. If being treated, no change in drug treatment within last 3 months;
  4. Advanced chronic renal impairment;
  5. Significant liver disease e.g. cirrhosis (fatty liver disease allowed);
  6. Malignancy which is currently active or in remission for less than five years after last treatment (local basal and squamous cell skin cancer allowed);
  7. Active inflammatory bowel disease, celiac disease, chronic pancreatitis or other disorder potentially causing malabsorption;
  8. Previous bariatric surgery;
  9. Chronic respiratory, neurological, musculoskeletal or other disorders where, in the judgement of the investigator, participants would have unacceptable risk or difficulty in complying with the protocol (e.g. physical activity program);
  10. A recent surgical procedure until after full convalescence (investigators judgement);
  11. Transmissible blood-borne diseases e.g. hepatitis B, HIV;
  12. Psychiatric illness (e.g. major depression, bipolar disorder).

    Medication:

  13. Use currently or within the previous 3 months of prescription medication that has the potential of affecting body weight or glucose metabolism such as glucocorticoids (but excluding inhaled and topical steroids; bronchodilators are allowed), psychoactive medication, epileptic medication, or weight loss medications (either prescription, over the counter or herbal). Low dose antidepressants are allowed if they, in the judgement of the investigator, do not affect weight or participation to the study protocol. Levothyroxine for treatment of hypothyroidism is allowed if the participant has been on a stable dose for at least 3 months.

    Personal/Other:

  14. Engagement in competitive sports;
  15. Self-reported weight change of >5 % (increase or decrease) within 2 months prior to screening;
  16. Special diets (e.g. vegan, Atkins) within 2 months prior to study start. A lacto-vegetarian diet is allowed;
  17. Severe food intolerance expected to interfere with the study;
  18. Regularly drinking > 21 alcoholic units/week (men), or > 14 alcoholic units/week (women);
  19. Use of drugs of abuse within the previous 12 months;
  20. Blood donation or transfusion within the past 1 month before baseline or CID's;
  21. Self-reported eating disorders;
  22. Pregnancy or lactation, including plans to become pregnant within the next 36 months.
  23. No access to either phone or Internet (this is necessary when being contacted by the instructor's during the maintenance phase);
  24. Adequate understanding of national language;
  25. Psychological or behavioral problems which, in the judgement of the investigator, would lead to difficulty in complying with the protocol.

    Laboratory screening:

    If all of the above criteria are satisfied, the participant is eligible for a glucose tolerance test (blood at 0 and 120 mins), and blood glucose concentrations are analyzed immediately (Haemocue). In addition full blood count, urea, and electrolytes may be analyzed as a further safety evaluation.

    ONLY IF the glucose tolerance test meets the entry criteria for the study, the remaining samples are sent to the local laboratory for a safety check, with the following exclusion criteria:

  26. Hemoglobin concentration below local laboratory reference values (i.e. anemia).
  27. Creatinine >1.5 times Upper Limit of Normal (local laboratory reference values).
  28. Alanine Transaminase (ALT) and/or Aspartate Transaminase (AST) >3 times the Upper Limit of Normal (local laboratory reference values) Or any other significant abnormality on these tests which in the investigators opinion may be clinically significant and require further assessment
  29. Electrocardiography (ECG). Any abnormality which in the opinion of the investigator might indicate undiagnosed cardiac disease requiring further assessment (e.g. significant conduction disorder, arrhythmia, pathological Q waves). This is done in adults 55-70 years of age.

    After LCD phase (in adults):

  30. Failure to reach at least 8% weight reduction during the LCD phase. This leads to exclusion from the intervention.
Both
10 Years to 70 Years
Yes
Contact: Anne B Raben, Professor +4535333653 ara@life.ku.dk
Contact: Thomas M Larsen, Associate professor +4535332505 tml@life.ku.dk
Australia,   Bulgaria,   Denmark,   Finland,   Netherlands,   New Zealand,   Spain,   United Kingdom
 
NCT01777893
B303, 312057
Yes
Anne Birgitte Raben, University of Copenhagen
Anne Birgitte Raben
  • Helsinki University
  • Maastricht University
  • University of Nottingham
  • University of Navarra
  • Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria
  • University of Sydney
  • University of Auckland, New Zealand
  • University of Stuttgart
  • Swansea University
  • Cambridge Manufacturing Company Limited
  • European Union
Principal Investigator: Thomas M Larsen, Associate Professor University of Copenhagen
Principal Investigator: Mikael Fogelholm, Professor Helsinki University
Principal Investigator: Margriet Westerterp-Plantenga, Professor Maastricht University
Principal Investigator: Ian McDonald, Professor University of Nottingham Medical School
Principal Investigator: J. Alfredo Martinez, Professor University of Navarra
Principal Investigator: Svetoslav Handjiev, Professor Medical University Sofia
Principal Investigator: Jennie Brand-Miller, Professor University of Sydney
Principal Investigator: Sally D. Poppitt, Professor University of Auckland, New Zealand
University of Copenhagen
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP