Condition category
Nutritional, Metabolic, Endocrine
Date applied
31/05/2017
Date assigned
31/05/2017
Last edited
12/06/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Diabetes is a common chronic condition. About 6% of the UK population already have either type 1 diabetes (T1DM) or type 2 diabetes (T2DM), and one in ten adults are at risk of developing diabetes. People may develop problems due to diabetes, including diabetic eye disease, numbness in feet, kidney damage and heart problems. However, diabetes can also cause other problems that are not as easy to prevent or treat such as delayed stomach emptying after meals, and problems with the pancreas not producing enough juices to help digest food. When the pancreas doesn’t produce enough of these digestive juices, patients may have gastrointestinal (stomach and intestine) symptoms including abdominal pain, bloating, diarrhoea and weight loss. This condition is called pancreatic exocrine insufficiency (PEI) and it is confirmed by doing a stool test. It is easily treated by replacing the digestive juices in a capsule, which contains enzymes for digestion (pancreatic enzyme replacement therapy – PERT). This is taken with every meal and snack and can significantly improve symptoms. This treatment may also improve blood sugar levels for people with diabetes, but we are not sure exactly how this happens. Measuring sugar levels with finger-prick tests or with HbA1c (a measure of average glucose levels over a 6 week period) does not clearly show these changes in sugar levels. The aim of this study is to find out more about how pancreatic enzyme replacement therapy may have an effect on sugar levels in patients who also have diabetes by using a new way of measuring sugar levels called a continuous glucose monitor which will measure sugar levels in much more detail.

Who can participate?
Adults aged 18 and older with either type 1 or type 2 diabetes, who have recently been diagnosed with PEI but who have not yet started treatment for this.

What does the study involve?
Participants attend four study visits. At the first visit, participants fill out a questionnaire about their gastrointestinal symptoms and have a blood test. They receive a continuous glucose monitor (a small disc that sticks to the back of the arm with a tiny fibre that is inserted under the skin) for two weeks. Participants check their blood sugar levels normally. After two weeks, participants are given a prescription for Creon. They take this for six weeks and then have another continuous glucose monitor applied for two weeks. At the last visit, the sensor is removed and participants repeat the blood test and questionnaire.

What are the possible benefits and risks of participating?
Participants may benefit by receiving a treatment which may improve their gastrointestinal symptoms. Depending on the outcome of the study, participants may also improve their sugar levels. There are no notable risks with participating as Creon is a safe drug that has been used in the NHS for several years. We are using Creon in this study in the same way as we would for people with PEI who do not have diabetes, so even after the study, or if patients decide not to take part, we will still recommend that patients take Creon. The most common side effects of Creon are gastrointestinal, but are normally due to the underlying PEI rather than the new drug. The safety of the continuous glucose monitor has been tested by the manufacturer. Occasionally the sticky patch can cause some skin itching or a mild rash. Participants may experience discomfort when providing blood samples.

Where is the study run from?
Queen Alexandra Hospital (UK)

When is the study starting and how long is it expected to run for?
March 2017 to July 2018

Who is funding the study?
Mylan Products Ltd

Who is the main contact?
Dr Katherine Alington
Katherine.alington@porthosp.nhs.uk

Trial website

N/A

Contact information

Type

Public

Primary contact

Dr Katherine Alington

ORCID ID

http://orcid.org/0000-0003-4547-8158

Contact details

Academic Department of Diabetes and Endocrinology
Queen Alexandra Hospital
Southwick Hill Road
Portsmouth
PO6 3LY
United Kingdom
+44 2392 286260
katherine.alington@porthosp.nhs.uk

Type

Scientific

Additional contact

Prof Michael Cummings

ORCID ID

Contact details

Academic Department of Diabetes and Endocrinology
Queen Alexandra Hospital
Southwick Hill Road
Portsmouth
PO6 3LY
United Kingdom

Additional identifiers

EudraCT number

2017-001227-45

ClinicalTrials.gov number

Protocol/serial number

34410

Study information

Scientific title

Comparison of ambulatory glucose profile prior to and during pancreatic enzyme replacement therapy in patients with diabetes and pancreatic exocrine insufficiency: A single-arm phase IV trial

Acronym

DRIVE - PEI

Study hypothesis

The aim of the study is to investigate whether treatment of pancreatic exocrine insufficiency in individuals with type 1 or type 2 diabetes mellitus results in improved glycaemic control.

Ethics approval

South Central – Hampshire B, 12/06/2017, 17/SC/0224

Study design

Non-randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Non randomised study

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

Specialty: Diabetes, Primary sub-specialty: Both; UKCRC code/ Disease: Metabolic and Endocrine/ Diabetes mellitus

Intervention

Participants all have type 1 or type 2 diabetes and will be newly diagnosed with pancreatic exocrine insufficiency. At the first visit, participants fill out a questionnaire about their gastrointestinal symptoms and have a blood test. Participants will wear a flash glucose monitoring sensor for 14 days to measure their baseline ambulatory glucose profile. They then commence therapy with Creon 50,000 units with meals and 25,000 units with snacks, in accordance with standard care for patients diagnosed with pancreatic exocrine insufficiency. All participants will receive the same drug and at the same dose for the same duration. Participants check their blood sugar levels normally during this time. After continuing Creon for 6 weeks, participants have a repeat flash glucose monitoring sensor applied for 14 days and the ambulatory glucose profile metrics will be compared. Improvement in symptoms will be assessed using a gastrointestinal symptom questionnaire. Additional clinical measurements including HbA1c and BMI will be taken at baseline and at 8 weeks.

Intervention type

Drug

Phase

Phase IV

Drug names

Creon

Primary outcome measures

Mean glucose interquartile range measured over 14 days at baseline (weeks 0-2) and after pancreatic enzyme replacement therapy (PERT) (at weeks 8-10) as measured using the Freestyle Libre Pro flash glucose monitor.

Secondary outcome measures

1. Other ambulatory glucose profile (AGP) metrics averaged over 14 days as measured by the Freestyle Libre flash glucose monitor at weeks 6-8 of PERT therapy:
1.1. Area under the median curve (AUC)
1.2. Median
1.3. Time above target range (above 10mmol/L and above 15mmol/L)
1.4. Time in target range (TIR) (4-10mmol/L)
1.5. Time below target range (below 4mmol/L and below 3mmol/L)
1.6. Median curve instability
1.7. Specific time periods – including pre-prandial and post-prandial
1.8. Estimated HbA1c
2. GI symptoms are measured using a questionnaire at 8 weeks after starting PERT
3. Clinical measurements – HbA1c, weight, BMI are measured using venous blood sampling and physical examination at 8 weeks after starting PERT

Overall trial start date

18/03/2017

Overall trial end date

31/07/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male or Female, aged 18 years or above
2. Diagnosed with Type 1 diabetes or Type 2 diabetes at least 1 year ago, and be receiving oral and / or insulin therapy for diabetes
3. Have 1 or more symptoms of PEI:
3.1. Diarrhoea – Bristol Stool Chart (see appendix) type 5, 6 or 7
3.2. Steatorrhoea or greasy, pale or offensive smelling stools
3.3. Weight loss
3.4. Abdominal pain or cramps
3.5. Bloating or increased flatulence
4. Low faecal elastase level <200mcg/g in last 2 years
5. Willing and able to give informed consent for participation in the study and for GP to be informed

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 20; UK Sample Size: 20

Participant exclusion criteria

1. Currently receiving, or have ever received, PERT
2. Current prescription of or planning to commence medication (within next 2 months), other than those for diabetes, that may increase or decrease serum glucose levels such as:
2.1. Oral corticosteroids for more than 7 days
2.2. Antipsychotics
2.3. Nutritional supplements such as Fresubin®
2.4. Weight-loss medication such as orlistat
3. Diagnosed with or suspected diagnosis of:
3.1. Pancreatic malignancy
3.2. Acute pancreatitis or chronic pancreatitis
3.3. Type 3c diabetes or other Type 3 secondary diabetes
3.4. Cystic fibrosis
3.5. Previous or awaited gastric bypass (within next 2 months), pancreatic or extensive small bowel surgery
3.6. Other primary pancreatic disorder or uncontrolled liver disorder (exception: non-alcoholic fatty liver disease)
4. Current or recently resolved (within 2 weeks) acute diarrhoeal episode thought likely to be infectious or other gastroenteritis
5. Current of previous chronic alcohol excess
6. Currently pregnant, recently postpartum (within 6 months) or planning pregnancy before end of study date
7. Currently using a modified diet under dietetic supervision, such as FODMAP
8. Currently receiving supported nutrition, including via nasogastric tube, gastrostomy tube or parenteral nutrition
9. Known allergy to Creon® or any of its components
10. Objection to porcine origin of pancreatin
11. Known allergy to Freestyle Libre Pro adhesive pad
12. Already enrolled, or recently (within 6 weeks) taken part in, another study that may affect glycaemic control or that may affect digestion or absorption or another aspect of the GI system or nutrition

Recruitment start date

01/06/2017

Recruitment end date

31/07/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Queen Alexandra Hospital
Portsmouth Hospitals NHS Trust
Portsmouth
PO6 3LY
United Kingdom

Sponsor information

Organisation

Portsmouth Hospitals NHS Trust

Sponsor details

De La Court House
Queen Alexandra Hospital
Southwick Hill Road
Portsmouth
PO6 3LY
United Kingdom

Sponsor type

Hospital/treatment centre

Website

www.porthosp.nhs.uk/departments/Research/research-innovation.htm

Funders

Funder type

Industry

Funder name

Mylan Products Ltd

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The results of the study will be submitted for publication in a peer-reviewed journal.


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

Intention to publish date

31/07/2019

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

12/06/217: Added Professor Cummings as a study contact. Added ethics approval, updated outcome measures and added the publication and diseemination plan, intention to publish date and individual participant data sharing plan.