Condition category
Nutritional, Metabolic, Endocrine
Date applied
08/08/2012
Date assigned
09/08/2012
Last edited
04/08/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and aims
Type 2 diabetes is regarded as an irreversible disease of the pancreas. It is now known that this is not true. A study performed in Newcastle has shown that people with short duration type 2 diabetes can regain normal blood sugar (glucose) control after a period of strict dieting. This study will examine whether the reversal of diabetes using a very low calorie diet is possible in individuals with long duration diabetes as well as short duration disease. It will establish the sustainability of the reversal of type 2 diabetes, and the best approach to maintaining the beneficial effects of this period of dieting using longer term lifestyle modification. Finally, the mechanisms behind the reversal of diabetes will be defined, looking in particular at the effect of fat on the pancreas. By using MRI scans of the pancreas and liver, along with tests using glucose and insulin, the effect of fat in the 'wrong' place will be defined. Together, this information would be of enormous importance to all people with type 2 diabetes, improving our understanding of the condition and exploring the potential of a medication-free treatment strategy.

Who can participate?
People aged between 25 and 80 years who have type 2 diabetes of less than 4 years or more than 8 years duration.

What does the study involve?
The research involves an 8-week period of very low calorie dieting to induce weight loss and improve blood glucose control. Participants will then be asked to follow a weight maintaining diet and physical activity plan for 6 months with education and support throughout. Detailed metabolic tests and magnetic resonance imaging (MRI) scans will be performed on three occasions with more regular, shorter visits throughout the 8-month study.

What are the possible benefits and risks from taking part in this study?
The weight loss achieved during the study is likely to bring substantial benefits to health. Participants will gain a better understanding of type 2 diabetes and its management. There are no major risks from taking part in this study. The very low calorie diet is safe under medical supervision. The intense dieting and longer term lifestyle change are challenging but full support will be given. Occasionally there may be some mild discomfort at the sites of the plastic tubes for a few hours after removal. The MRI scans are non-invasive, safe and do not use X-rays or any other harmful radiation. It makes a high-pitched sound and you will be given ear-muffs to wear. There is a very small risk (less than one in a million) of an allergic reaction to a substance used in the study called Intralipid. This only occurs in people who are allergic to soy protein or eggs so if you have these allergies you will not be able to take part in the study.

Where is the study run from?
Newcastle University (UK).

When is the study starting and how long is it expected to run for?
The study started in August 2012 and will run for 2 years.

Who is funding the study?
Novo Nordisk UK Research Foundation and the Newcastle NIHR Biomedical Research Centre.

Who is the main contact?
Dr Sarah Steven
sarah.steven@ncl.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Sarah Steven

ORCID ID

Contact details

Newcastle University
Institute for Ageing and Health
Campus for Ageing and Vitality
Newcastle upon Tyne
NE4 5PL
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

12627

Study information

Scientific title

Characterisation of the principle determinants of long term reversal of type 2 diabetes

Acronym

Study hypothesis

Restated hypothesis as of 31/07/2015:
Prevalence of Type 2 diabetes increases sharply with age. Our recent work has shown that the twin defects of insulin resistance and inadequate insulin secretion can be entirely reversed by short term calorie restriction resulting in long term withdrawal of oral hypoglycaemic agents and insulin. Three distinct questions must now be answered:
1. What is the interaction of duration of type 2 diabetes with reversibility?
2. Does dietary modification over 6 months protect the return to normal blood glucose control and beta cell function in the group achieving restoration of normality?
3. Does increased daily physical activity or increased monounsaturated fat intake enhance this protection?

Previous hypothesis:
Prevalence of Type 2 diabetes increases sharply with age. Our recent work has shown that the twin defects of insulin resistance and inadequate insulin secretion can be entirely reversed by short term calorie restriction resulting in long term withdrawal of oral hypoglycaemic agents and insulin. Three distinct questions must now be answered:
1. What is the interaction of duration of type 2 diabetes with reversibility?
2. Does dietary modification protect the beta cells from longer term deterioration of function after restoration of normality, as seen in vitro?
3. Does increased daily physical activity enhance this protection?

On 31/07/2015 the overall trial end date was changed from 01/09/2013 to 30/06/2014.

Ethics approval

Newcastle and North Tyneside 2 Research Ethics Committee, 22/06/2012, ref: 12/NE/0208

Study design

Randomised interventional trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Diabetic Control, Nutrition, Obesity

Intervention

Restated interventions as of 31/07/2015:
Dietary modification, Very low calorie diet; Physical activity, Increased physical activity levels.
The weight maintenance interventions are of 6 months duration and primarily involve a level of calorie intake to maintain weight steady. The randomised sub-study tests involve either a high monounsaturated fat diet or usual diet, and increased physical activity or usual physical activity.

Previous interventions:
Dietary modification, Very low calorie diet; Physical activity, Increased physical activity levels.
The weight maintenance interventions are of 6 months duration and involve either a high monounsaturated fat diet or usual diet, and increased physical activity or usual physical activity.

Intervention type

Behavioural

Phase

Drug names

Primary outcome measures

Restated primary outcome measures as of 31/07/2015:
Fasting plasma glucose at 6 months in the group achieving non-diabetic levels at 10 weeks (following VLCD and return to normal eating)

Previous primary outcome measures:
Beta cell function measured at baseline, 8 weeks and 8 months

Secondary outcome measures

Added 31/07/2015:
Change in beta cell function from 10 weeks to 6 months

Overall trial start date

20/07/2012

Overall trial end date

30/06/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Type 2 diabetes of < 4 years or > 8 years duration
2. HbA1c < 80 mmol/l / 9.5%
3. BMI 28-40kg/m2
4. Age 25-80 years
5. Stable weight for previous 6 months (within 5kg)
6. Male and female participants

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

UK Sample Size: 34

Participant exclusion criteria

1. Current treatment with thiazolidinediones, GLP-1 agonists or steroids
2. Renal or hepatic dysfunction
3. Contraindications to MRI
4. Alcohol consumption > 3 units per day for women and > 4 units per day for men
5. Allergy to soybean or eggs
6. Highly restrictive diet

Recruitment start date

31/08/2012

Recruitment end date

11/09/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Newcastle University
Newcastle upon Tyne
NE4 5PL
United Kingdom

Sponsor information

Organisation

Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)

Sponsor details

Midwifery Research Department
Leazes Wing
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.newcastle-hospitals.org.uk/

Funders

Funder type

Government

Funder name

National Institute of Health Research [NIHR] - Biomedical Research Centre (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Novo Nordisk UK Research Foundation

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25683066

Publication citations

Additional files

Editorial Notes