Neonatal DiabetesFoNDNCT02921906
Effect of Food Composition on Postprandial Insulin Secretion in Neonatal Diabetes
A study testing High protein meal, High carbohydrate meal and Paracetamol in people with Neonatal Diabetes, run by Royal Devon and Exeter NHS Foundation Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 years and olderHealthy volunteers can take part
- Conditions the study is for
- Neonatal Diabetes
- What is being tested?
- High protein meal, High carbohydrate meal and Paracetamol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2016to 20 Jun 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Exeter Clinical Research Facility
Exeter, Devon, EX25DW
About this study
Official title: Assessing the Effect of Food Composition on Postprandial Insulin Secretion in KCNJ11 Neonatal Diabetes (FoND Study)
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.
Read the 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.
- Conditions
- Neonatal Diabetes
- Being tested
- High protein meal, High carbohydrate meal, Paracetamol, Fasting state - sulphonylurea only
- Keywords
- Insulin, Glucose, Incretin, GLP-1, Food
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High protein mealOther
Breakfast with high protein / low carbohydrate content
High carbohydrate mealOther
Breakfast with high carbohydrate / low protein content
ParacetamolDrug
Also called Acetaminophen
Standard dose of paracetamol administered with each meal to allow measurement of rate of gastric emptying.
Fasting state - sulphonylurea onlyOther
People with diabetes take sulphonylurea medication in the absence of any food stimulus
| Study group | Role | What they receive |
|---|---|---|
| Neonatal diabetes | Experimental | People with neonatal diabetes due to mutations in the KCNJ11 gene who are treated with sulphonylureas and not on insulin. Receives: Other: High protein meal; Other: High carbohydrate meal; Drug: Paracetamol; Other: Fasting state - sulphonylurea only |
| Non-diabetic controls | Active comparator | People without diabetes. Receives: Other: High protein meal; Other: High carbohydrate meal; Drug: Paracetamol |
| Controls with Type 2 Diabetes | Active comparator | People with Type 2 diabetes who are treated with sulphonylurea medication. Receives: Other: High protein meal; Other: High carbohydrate meal; Drug: Paracetamol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucose levels
Glucose AUC after each meal.
Measured: 240 minutes
Insulin levels
Insulin AUC after each meal.
Measured: 240 minutes
Secondary outcomes (4)
GLP-1 levels
GLP-1 AUC after each meal.
Measured: 240 minutes
GIP levels
GIP AUC after each meal.
Measured: 240 minutes
Glucagon levels
Glucagon AUC after each meal.
Measured: 240 minutes
Paracetamol levels
Rate of change of paracetamol levels after each meal as marker of gastric emptying.
Measured: 240 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2016 (estimated)
- Study startJun 2016
- Primary completion20 Jun 2022
- Study completion20 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neonatal DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Devon and Exeter NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew T Hattersley, BMBCh DM FRS, Study chair, University of Exeter
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02921906
- Sponsor's protocol ID
- R&D no 1701366
- Acronym
- FoND
- Status last verified
- Oct 2022
- First submitted
- 20 Sep 2016
- Last updated
- 31 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Bowman P, McDonald TJ, Knight BA, Flanagan SE, Leveridge M, Spaull SR, Shields BM, Hammersley S, Shepherd MH, Andrews RC, Patel KA, Hattersley AT. Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-KATP-channel pathways. BMJ Open Diabetes Res Care. 2019 Dec 18;7(1):e000721. doi: 10.1136/bmjdrc-2019-000721. eCollection 2019.
PubMed 31908791
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing the Effect of Food Composition on Postprandial Insulin Secretion in KCNJ11 Neonatal Diabetes (FoND Study)
- ClinicalTrials.gov ID
- NCT02921906
- Acronym / sponsor ID
- FoND / R&D no 1701366
- Conditions
- Neonatal Diabetes
- Keywords
- Insulin, Glucose, Incretin, GLP-1, Food
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Royal Devon and Exeter NHS Foundation TrustUniversity, hospital or other
- Study start
- Jun 2016
- Primary completion
- 20 Jun 2022 (actual)
- Study completion
- 20 Jun 2022 (actual)
- First posted
- 3 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Neonatal diabetes | Experimental | Other: High protein meal, Other: High carbohydrate meal, Drug: Paracetamol, Other: Fasting state - sulphonylurea onlyPeople with neonatal diabetes due to mutations in the KCNJ11 gene who are treated with sulphonylureas and not on insulin. |
| Non-diabetic controls | Active comparator | Other: High protein meal, Other: High carbohydrate meal, Drug: ParacetamolPeople without diabetes. |
| Controls with Type 2 Diabetes | Active comparator | Other: High protein meal, Other: High carbohydrate meal, Drug: ParacetamolPeople with Type 2 diabetes who are treated with sulphonylurea medication. |
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (4 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High protein mealBreakfast with high protein / low carbohydrate content | Other | Controls with Type 2 Diabetes, Neonatal diabetes, Non-diabetic controls |
| High carbohydrate mealBreakfast with high carbohydrate / low protein content | Other | Controls with Type 2 Diabetes, Neonatal diabetes, Non-diabetic controls |
| ParacetamolAlso: AcetaminophenStandard dose of paracetamol administered with each meal to allow measurement of rate of gastric emptying. | Drug | Controls with Type 2 Diabetes, Neonatal diabetes, Non-diabetic controls |
| Fasting state - sulphonylurea onlyPeople with diabetes take sulphonylurea medication in the absence of any food stimulus | Other | Neonatal diabetes |
Primary outcome
Glucose levels
Time frame: 240 minutes
Glucose AUC after each meal.
Insulin levels
Time frame: 240 minutes
Insulin AUC after each meal.
4 secondary outcomes
GLP-1 levels
Time frame: 240 minutes
GIP levels
Time frame: 240 minutes
Glucagon levels
Time frame: 240 minutes
Paracetamol levels
Time frame: 240 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2022.
- Derived from this study: PubMed 31908791Bowman P, McDonald TJ, Knight BA, Flanagan SE, Leveridge M, Spaull SR, Shields BM, Hammersley S, Shepherd MH, Andrews RC, Patel KA, Hattersley AT. Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-KATP-channel pathways. BMJ Open Diabetes Res Care. 2019 Dec 18;7(1):e000721. doi: 10.1136/bmjdrc-2019-000721. eCollection 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew T Hattersley, BMBCh DM FRS study chair
University of Exeter
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High protein meal, High carbohydrate meal and Paracetamol in people with Neonatal Diabetes, run by Royal Devon and Exeter NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glucose levels (time frame: 240 minutes). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02921906, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2022.