Condition category
Nutritional, Metabolic, Endocrine
Date applied
20/08/2019
Date assigned
23/08/2019
Last edited
30/12/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Exercise mobilises endothelial progenitor cells (EPCs), a cell that circulates within the blood and plays a role in the repair and formation of new blood vessels in healthy individuals. Higher numbers of these cells are associated with better blood vessel function and reduced heart disease and are released into the circulation during and after exercise. While it is known that individuals with type 1 diabetes, older individuals and individuals with lower fitness levels have a reduced number of circulating EPCs at rest, it is not known what the response to exercise is in individuals with type 1 diabetes and to what extent clinical factors such as age, fitness level and inflammation influences the number of EPCs. This study will explore how numbers of EPCs at rest and after exercise differ between T1D and healthy participants, and will explore clinical factors that predict the numbers.

Who can participate?
Patients aged 18-65 with type 1 diabetes and age, sex and fitness-matched healthy volunteers

What does the study involve?
Participants with type 1 diabetes undergo a urine test and a mixed meal tolerance test. Both type 1 diabetes and healthy control participants undergo a graded exercise test before a fixed bout of moderate-intensity walking exercise for 45 minutes, with blood samples taken before, immediately after and 1 hour after the exercise to measure the numbers of EPCs in their blood.

What are the possible benefits and risks of participating?
Participants will find out about their individual responses to exercise, receive feedback on fitness, and contribute to the care and management of those with type 1 diabetes. The risks of taking part include experiencing low blood sugar, injury and muscle soreness.

Where is the study run from?
The study is being run by Newcastle University and takes place in the clinical research facility in the Royal Victoria Infirmary (UK)

When is the study starting and how long is it expected to run for?
October 2016 to September 2019

Who is funding the study?
1. Diabetes Research and Wellness Foundation (UK)
2. Newcastle University (UK)

Who is the main contact?
1. Dr Daniel West
Daniel.West@newcastle.ac.uk
2. Guy Taylor
G.Taylor3@newcastle.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Dr Daniel West

ORCID ID

http://orcid.org/0000-0003-2246-4925

Contact details

Institute of Cellular Medicine
Newcastle University
Newcastle Upon Tyne
NE2 4HH
United Kingdom
+44 (0)191 208 7076
daniel.west@ncl.ac.uk

Type

Public

Additional contact

Mr Guy Taylor

ORCID ID

http://orcid.org/0000-0002-5207-1498

Contact details

Institute of Cellular Medicine
Room M4.077
William Leech Building
Newcastle University
Newcastle Upon Tyne
NE2 4HH
United Kingdom
+44 (0)1912088264
g.taylor3@newcastle.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

V3 14/07/16

Study information

Scientific title

Endothelial progenitor cell (EPCs) response to exercise in individuals with and without type 1 diabetes

Acronym

Study hypothesis

Individuals with type 1 diabetes will have reduced numbers of EPCs and progenitor cells. Type 1 diabetes participants with higher residual beta-cell function, shorter duration of diabetes, younger age and better control will have increased numbers of these cells.

Ethics approval

1. Approved 02/09/2016, North East Tyne & Wear South Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Dr, Newcastle upon Tyne, NE2 4NQ; Tel: +44 (0)207 104 8026; Email: nrescommittee.northeast-tyneandwearsouth@nhs.net), ref: 16/NE/0192
2. Approved 04/06/2018, Faculty of Medical Science Ethics Committee (Research & Innovation office, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH; Tel: +44 (0)191 208 5301; Email: fmsethics@ncl.ac.uk), ref: 1516/5648/2018

Study design

Acute observational trial

Primary study design

Observational

Secondary study design

Comparison

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Type 1 diabetes

Intervention

30 patients with Type 1 diabetes with a wide range of ages, duration of diabetes, fitness, glycaemic control and residual beta-cell function will be recruited. Healthy controls who are age, gender and fitness matched will also be recruited. Type 1 diabetes participants will be identified using urinary C-peptide to Creatinine Ratio testing, and those eligible will complete a mixed meal tolerance test to establish maximal stimulated serum C-peptide concentrations. Both type 1 diabetes and healthy control participants will complete a graded exercise test to determine VO2peak before completing a fixed bout of moderate-intensity walking exercise at 60% VO2 peak for 45 minutes, with blood samples taken before, immediately after and 1 hour after the exercise.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Number of EPCs (CD34+, CD45dim, VEGFR2 and CD34+, CD45dim, CD31+) measured by flow cytometry pre, immediately post and 1-hour post the exercise test between type 1 diabetes and healthy controls

Secondary outcome measures

1. Clinical factors at baseline:
1.1. Fitness measured using graded exercise VO2peak test
1.2. Glycaemic control measured by CGM time in range/in hypoglycaemia/hyperglycaemia and glycaemic variability parameters and HbA1c via commercially available assay test
1.3. Residual beta cell function measured by stimulated serum C-peptide MMTT via commercially available assay test
2. Number of progenitor cells ( (1) CD34+ (2) CD34+, CD45dim (3) CD34+, CD45bright (4) CD34+, CD31+ (5) CD34+, VEGFR2+ (6) CD34+, CD45bright, CD31+ (7) CD34+, CD45bright, VEGFR2+) measured by flow cytometry pre, immediately post and 1-hour post the exercise test in participants with type 1 diabetes and healthy controls
3. Number of EPCs and progenitors expressing chemokine receptors (CXCR4, CXCR7) and the Mean Fluorescence Intensity (MFI) of these chemokine receptors measured using flow cytometry pre, immediately post and 1-hour post the exercise test in type 1 diabetes and healthy control participants

Overall trial start date

01/10/2016

Overall trial end date

30/09/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

T1D:
1. Aged 18-65 years old
2. Diagnosed with T1D
3. Treated with exogenous insulin (pump or injection)
4. Free from diabetes complications

Healthy:
1. Aged 18-65 years old
2. Free from any chronic diseases

Participant type

Mixed

Age group

Adult

Gender

Both

Target number of participants

Total n = 60 (T1D: 30 Control: 30)

Total final enrolment

60

Participant exclusion criteria

Cardiovascular disease or detection via ECG screening

Recruitment start date

01/11/2016

Recruitment end date

01/07/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Newcastle upon Tyne NHS Foundation Trust
Level 1 Regent Point Gosforth
Newcastle upon Tyne
NE3 3HD
United Kingdom

Sponsor information

Organisation

Newcastle University

Sponsor details

Faculty of Medical Sciences
The Medical School
Framlington Place
Newcastle upon Tyne
NE2 4HH
United Kingdom
+44 (0)191 208 6000
kay.howes@ncl.ac.uk

Sponsor type

University/education

Website

https://www.ncl.ac.uk/

Funders

Funder type

University/education

Funder name

Diabetes Research and Wellness Foundation

Alternative name(s)

Diabetes Research and Wellness Foundation UK, DRWF

Funding Body Type

private sector organisation

Funding Body Subtype

Trusts, charities, foundations (both public and private)

Location

United Kingdom

Funder name

Faculty of Medical Sciences, Newcastle University

Alternative name(s)

FMS

Funding Body Type

private sector organisation

Funding Body Subtype

Universities (academic only)

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal.

IPD sharing statement:
The current data sharing plans for this study are unknown and will be available at a later date

Intention to publish date

01/05/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

30/12/2019: Internal review. 11/12/2019: Internal review. 10/12/2019: Internal review. 22/08/2019: Trial's existence confirmed by ethics committee.