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Trial record 2 of 8 for:    KCNJ11

Effect of Food Composition on Postprandial Insulin Secretion in Neonatal Diabetes (FoND)

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ClinicalTrials.gov Identifier: NCT02921906
Recruitment Status : Unknown
Verified July 2017 by Royal Devon and Exeter NHS Foundation Trust.
Recruitment status was:  Recruiting
First Posted : October 3, 2016
Last Update Posted : July 6, 2017
Sponsor:
Information provided by (Responsible Party):
Royal Devon and Exeter NHS Foundation Trust

Brief Summary:
Neonatal diabetes is diagnosed before 6 months of age and causes high blood glucose levels due to the pancreas not secreting insulin. Neonatal diabetes can be caused by a change in a DNA region called the KCNJ11 gene. KCNJ11 encodes a channel in the pancreas that acts as a switch to turn 'on' and 'off' insulin secretion. A change in KCNJ11 results in a faulty channel, which keeps insulin secretion 'switched off'. The diabetes can be treated with tablets called sulphonylureas that switch the pancreatic channel 'on', allowing it to secrete insulin in response to gut hormones called incretins. Previous research has shown that patients who switch from insulin to sulphonylureas have better blood glucose control, including fewer episodes of hypoglycaemia (glucose dropping too low), and also avoid the need for injections. It is thought that serious side effects from sulphonylureas are uncommon in KCNJ11 neonatal diabetes. Some patients report low glucose after meals and we think this may be because they make too much insulin if they eat a meal with protein but low amounts of carbohydrate. The investigators will test this by giving study participants different meals and measuring the amount of insulin, glucose and incretin hormone in the blood afterwards.

Condition or disease Intervention/treatment Phase
Neonatal Diabetes Other: High protein meal Other: High carbohydrate meal Drug: Paracetamol Other: Fasting state - sulphonylurea only Not Applicable

Detailed Description:
Anecdotal evidence from routine clinical care suggests that patients with sulphonylurea-treated KCNJ11 neonatal diabetes, when they eat, may experience mild hypoglycaemia if the food consumed lacks carbohydrate. It has been suggested that this may be due to regulation of insulin secretion via the incretin pathway as opposed to the classical ATP pathway. Therefore the investigators hypothesise that foods with a relatively high protein content compared to those with a relatively high carbohydrate content will result in excessive insulin secretion and relatively lower glucose values in KCNJ11 patients. This would be in contrast to healthy control subjects or subjects with SU-treated T2D where the insulin secretion will be moderated by the ambient glucose via the classical ATP pathway. The investigators will formally study this hypothesis by comparing the insulin, glucose and incretin hormone responses to a high protein meal with a high carbohydrate meal in people with KCNJ11 neonatal diabetes, people without diabetes and people with sulphonylurea-treated Type 2 Diabetes. To assess whether any effect seen is due to direct stimulation of the beta cell by the sulphonylurea itself, people with KCNJ11 neonatal diabetes will also undergo the same tests in the fasting state, having taken the sulphonylurea in the absence of any food.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Assessing the Effect of Food Composition on Postprandial Insulin Secretion in KCNJ11 Neonatal Diabetes (FoND Study)
Study Start Date : June 2016
Estimated Primary Completion Date : May 2018
Estimated Study Completion Date : August 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Insulin

Arm Intervention/treatment
Experimental: Neonatal diabetes
People with neonatal diabetes due to mutations in the KCNJ11 gene who are treated with sulphonylureas and not on insulin.
Other: High protein meal
Breakfast with high protein / low carbohydrate content

Other: High carbohydrate meal
Breakfast with high carbohydrate / low protein content

Drug: Paracetamol
Standard dose of paracetamol administered with each meal to allow measurement of rate of gastric emptying.
Other Name: Acetaminophen

Other: Fasting state - sulphonylurea only
People with diabetes take sulphonylurea medication in the absence of any food stimulus

Active Comparator: Non-diabetic controls
People without diabetes.
Other: High protein meal
Breakfast with high protein / low carbohydrate content

Other: High carbohydrate meal
Breakfast with high carbohydrate / low protein content

Drug: Paracetamol
Standard dose of paracetamol administered with each meal to allow measurement of rate of gastric emptying.
Other Name: Acetaminophen

Active Comparator: Controls with Type 2 Diabetes
People with Type 2 diabetes who are treated with sulphonylurea medication.
Other: High protein meal
Breakfast with high protein / low carbohydrate content

Other: High carbohydrate meal
Breakfast with high carbohydrate / low protein content

Drug: Paracetamol
Standard dose of paracetamol administered with each meal to allow measurement of rate of gastric emptying.
Other Name: Acetaminophen




Primary Outcome Measures :
  1. Glucose levels [ Time Frame: 240 minutes ]
    Glucose AUC after each meal.

  2. Insulin levels [ Time Frame: 240 minutes ]
    Insulin AUC after each meal.


Secondary Outcome Measures :
  1. GLP-1 levels [ Time Frame: 240 minutes ]
    GLP-1 AUC after each meal.

  2. GIP levels [ Time Frame: 240 minutes ]
    GIP AUC after each meal.

  3. Glucagon levels [ Time Frame: 240 minutes ]
    Glucagon AUC after each meal.

  4. Paracetamol levels [ Time Frame: 240 minutes ]
    Rate of change of paracetamol levels after each meal as marker of gastric emptying.



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Ages Eligible for Study:   8 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age ≥8yrs.
  • Willing and able to provide informed consent (adults i.e. participants aged >16 years).
  • Willing and able to provide assent and parents willing to provide informed consent (children and young people <16 years).

Exclusion Criteria:

  • Age <8yrs.
  • Unable/unwilling to provide informed consent (adults).
  • Unable/unwilling to provide assent (children) or parents unwilling to provide informed consent.
  • Known liver disease or chronic renal impairment (EGFR <60ml/min).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02921906


Contacts
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Contact: Pamela Bowman, MBBS MA 01392408325 P.Bowman@exeter.ac.uk
Contact: Bea A Knight, PhD 01392408172 B.A.Knight@exeter.ac.uk

Locations
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United Kingdom
Exeter Clinical Research Facility Recruiting
Exeter, Devon, United Kingdom, EX25DW
Contact: Pamela Bowman, MBBS MA    01392408325    P.Bowman@exeter.ac.uk   
Contact: Bea A Knight, PhD    01392408172    B.A.Knight@exeter.ac.uk   
Sponsors and Collaborators
Royal Devon and Exeter NHS Foundation Trust
Investigators
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Study Chair: Andrew T Hattersley, BMBCh DM FRS University of Exeter

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Responsible Party: Royal Devon and Exeter NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT02921906     History of Changes
Other Study ID Numbers: R&D no 1701366
First Posted: October 3, 2016    Key Record Dates
Last Update Posted: July 6, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Royal Devon and Exeter NHS Foundation Trust:
Insulin
Glucose
Incretin
GLP-1
Food
Additional relevant MeSH terms:
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Infant, Newborn, Diseases
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Acetaminophen
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antipyretics