Type 1 DiabetesPhase 4NCT01488136
Use of Diazoxide in Acute Hypoglycaemia
A Phase 4 study testing Diazoxide in people with Type 1 Diabetes, run by University of Dundee at 1 site in United Kingdom.
Trial summary
The investigators know that intensive insulin therapy and tight glucose control is associated with reduction of diabetic complications. However, many patients on insulin don't achieve this because of the risk and the fear of hypoglycaemia (too low blood glucose). Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Diazoxide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2012to Mar 2013
- Phase
- Phase 4
- 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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Healthy adults (aged 18-55) with >5 years disease duration
- On intensive insulin therapy (CSII or multiple daily injections)
- HbA1C<8.0%
- Ability to give written informed consent to participate in the study
- BMI between 20-29
Who cannot join
- History of significant cardiac, hepatic, renal or neurological disease.
- Significant head injury, epilepsy or hypoglycaemia-induced seizures.
- Pregnancy.
- Breast feeding mothers.
- Participants on thiazide diuretics
- Participants on other potassium channel openers (nicorandil, minoxidil)
Show all 12Show fewer
- Participants on medications with vasodilatory properties such as methyldopa, reserpine, theophyllines and nitrites.
- Participants on hydantoins (fosphenytoin, phenytoin)
- Significant anaemia Hb<11.0 and Hct<33%.
- If they have donated blood in the last 30 days.
- All those who have participated in a CTIMP in the last 3 months
- Participants who are already on diazoxide or who have a past history of allergy to diazoxide
Trial locations and contacts
1 site in 1 country.
About this study
The investigators know that intensive insulin therapy and tight glucose control is associated with reduction of diabetic complications. However, many patients on insulin don't achieve this because of the risk and the fear of hypoglycaemia (too low blood glucose).
There has been a lot of work done recently looking at the mechanisms by which the brain detects hypoglycaemia. A key player is a potassium channel in the brain (KATP channel). Studies have shown that when these channels are opened, there is a release of hormones such as adrenaline that can help in raising blood sugars to counteract and increase awareness of hypoglycaemia. The investigators study aims to look at an old drug called diazoxide, which is able to open KATP channels.
Read more
The investigators aim to see if diazoxide will amplify the release of hormones such as adrenaline when the blood sugar is low. If this is the case, this will aid quicker recovery following hypoglycaemia.
The investigators aim to do this by performing a well established experimental protocol that has been performed safely over the last 20 years called a clamp study. The clamp study will involve slowly bringing the blood sugars down using insulin and intravenous glucose in a controlled fashion. The main outcome will be the hormonal responses (adrenaline response) at a blood sugar level of 2.5mmol/L. Symptoms of hypoglycaemia will be monitored, as well as working memory tests using standardised questionnaires.
The design of the investigators study will be a randomised trial comparing the effects of diazoxide with placebo in which all patients will receive both diazoxide and placebo in random order (crossover design).
Read the detailed description
This will be conducted in a double blinded (neither subject nor the researcher will know the order of the IMP(drug/placebo). All subjects will receive both the active drug and placebo in a random fashion (crossover design).
Once identified, patients will be given a participant information sheet. They will be contacted at a later date (minimum 24 hours) to determine if they are willing to participate in the trial.
Subjects will then be consented, and attend a screening visit, where it will be ascertained whether they fit the inclusion/exclusion criteria. Further details of the study will also be given to them at this visit. They will then attend a few days before the first study, and will be shown how to use the continuous glucose monitor which will measure their glucose overnight, prior to the start of the study. The reason for this, is that if they have very low blood sugars the night before the study, this can influence the results of the study, and they will be given an alternative day to attend. Provided they have been free of any hypoglycaemic episodes, the night before, they can then proceed with the study.
On the day of the study,we will place two intravenous cannulae. The cannulae in the hand vein will be placed in a warm chamber, in order to make it more more reflective of sampling at the blood brain barrier.
The subject will either have the investigational medicinal product (diazoxide) or placebo. Blood pressure and heart rate will be monitored throughout the clamp study. After 2 hours, with the use of insulin and dextrose, the subject's blood sugar will be brought to near normal and kept there for 40 minutes. After this, the blood sugar will be dropped in stages, until a blood sugar of 2.5mmol/L is reached. The blood sugar will be monitored very closely, with 5 minute sampling taken through one of the cannulue in situ, to avoid repeated stabbing. Also at regular intervals, blood samples will be taken for measurement of hormones, including adrenaline. At each stage, subjects will be asked about symptoms they are experiencing and a series of verbal working memory tests will also be performed.
- Conditions
- Type 1 Diabetes
- Being tested
- Diazoxide, Placebo
- Keywords
- Type 1 diabetes, Hypoglycaemia, Diazoxide
- Medical subject headings
- Diabetes Mellitus, Type 1, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DiazoxideDrug
Also called Eudemine (Diazoxide)
Diazoxide 7mg/kg, given 2 hours before the start of the clamp study
PlaceboDrug
Also called Lactose Ph capsules (Placebo)
Lactose Ph capsules (Placebo)
| Study group | Role | What they receive |
|---|---|---|
| Diazoxide | Active comparator | Oral diazoxide 7 mg/kg Receives: Drug: Diazoxide |
| Placebo | Placebo comparator | Matched placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adrenaline response(pmol/L) at 2.5mmol/L of glucose
The body secretes hormones such as adrenaline as a response to low blood sugars. Patients who have had insulin-dependant diabetes for over 5 years rely heavily on adrenaline release, to produce symptoms, so that they can respond appropriately to low blood sugars. However, this response is blunted in those with type 1 diabetes.
Our question is whether the magnitude of this response can be increased by use of diazoxide in the context of hypoglycaemia, so that patients with insulin-dependant diabetes become better aware of hypoglycaemia.
Measured: 1 year
Secondary outcomes (1)
Glucose Thresholds (calculated when counter-regulatory hormone release is greater than 2SD of hormone level at euglycaemia 4.0mmol/L blood sugar) of each of the counter-regulatory hormones (adrenaline, noradrenalin, glucagon)
Our study design enables us to bring down the blood sugar in a controlled fashion and maintain it at certain levels. We will be measuring hormones including adrenaline and testing cognitive function as well as assessing symptoms at each of these blood sugar levels. We want to see if diazoxide affects the threshold at which patients are able to mount a clinically relevant rise in counter-regulatory hormones and symptoms of hypoglycaemia.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2011 (estimated)
- Study startJan 2012
- Primary completionMar 2013
- Study completionMar 2013
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 Type 1 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation
- Responsible party
- Sponsor
- Investigators
- Rory J McCrimmon, MD, Study chair, Clinical ReaderPriya S George, MRCP, Principal investigator, Clinical Research Fellow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01488136
- Sponsor's protocol ID
- 2010DM03
- Other IDs
- 2011-005011-93
- Status last verified
- Oct 2019
- First submitted
- 26 Oct 2011
- Last updated
- 14 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
George PS, Tavendale R, Palmer CN, McCrimmon RJ. Diazoxide improves hormonal counterregulatory responses to acute hypoglycemia in long-standing type 1 diabetes. Diabetes. 2015 Jun;64(6):2234-41. doi: 10.2337/db14-1539. Epub 2015 Jan 15.
PubMed 25591873
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Diazoxide in Acute Hypoglycaemia
- ClinicalTrials.gov ID
- NCT01488136
- Acronym / sponsor ID
- 2010DM03
- Conditions
- Type 1 Diabetes
- Keywords
- Type 1 diabetes, Hypoglycaemia, Diazoxide
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation
- Study start
- Jan 2012
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 8 Dec 2011 (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.
The investigators know that intensive insulin therapy and tight glucose control is associated with reduction of diabetic complications. However, many patients on insulin don't achieve this because of the risk and the fear of hypoglycaemia (too low blood glucose).
There has been a lot of work done recently looking at the mechanisms by which the brain detects hypoglycaemia. A key player is a potassium channel in the brain (KATP channel). Studies have shown that when these channels are opened, there is a release of hormones such as adrenaline that can help in raising blood sugars to counteract and increase awareness of hypoglycaemia. The investigators study aims to look at an old drug called diazoxide, which is able to open KATP channels.
The investigators aim to see if diazoxide will amplify the release of hormones such as adrenaline when the blood sugar is low. If this is the case, this will aid quicker recovery following hypoglycaemia.
The investigators aim to do this by performing a well established experimental protocol that has been performed safely over the last 20 years called a clamp study. The clamp study will involve slowly bringing the blood sugars down using insulin and intravenous glucose in a controlled fashion. The main outcome will be the hormonal responses (adrenaline response) at a blood sugar level of 2.5mmol/L. Symptoms of hypoglycaemia will be monitored, as well as working memory tests using standardised questionnaires.
The design of the investigators study will be a randomised trial comparing the effects of diazoxide with placebo in which all patients will receive both diazoxide and placebo in random order (crossover design).
Detailed description
This will be conducted in a double blinded (neither subject nor the researcher will know the order of the IMP(drug/placebo). All subjects will receive both the active drug and placebo in a random fashion (crossover design).
Once identified, patients will be given a participant information sheet. They will be contacted at a later date (minimum 24 hours) to determine if they are willing to participate in the trial.
Subjects will then be consented, and attend a screening visit, where it will be ascertained whether they fit the inclusion/exclusion criteria. Further details of the study will also be given to them at this visit. They will then attend a few days before the first study, and will be shown how to use the continuous glucose monitor which will measure their glucose overnight, prior to the start of the study. The reason for this, is that if they have very low blood sugars the night before the study, this can influence the results of the study, and they will be given an alternative day to attend. Provided they have been free of any hypoglycaemic episodes, the night before, they can then proceed with the study.
On the day of the study,we will place two intravenous cannulae. The cannulae in the hand vein will be placed in a warm chamber, in order to make it more more reflective of sampling at the blood brain barrier.
The subject will either have the investigational medicinal product (diazoxide) or placebo. Blood pressure and heart rate will be monitored throughout the clamp study. After 2 hours, with the use of insulin and dextrose, the subject's blood sugar will be brought to near normal and kept there for 40 minutes. After this, the blood sugar will be dropped in stages, until a blood sugar of 2.5mmol/L is reached. The blood sugar will be monitored very closely, with 5 minute sampling taken through one of the cannulue in situ, to avoid repeated stabbing. Also at regular intervals, blood samples will be taken for measurement of hormones, including adrenaline. At each stage, subjects will be asked about symptoms they are experiencing and a series of verbal working memory tests will also be performed.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Diazoxide | Active comparator | Drug: DiazoxideOral diazoxide 7 mg/kg |
| Placebo | Placebo comparator | Drug: PlaceboMatched placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy adults (aged 18-55) with >5 years disease duration
- On intensive insulin therapy (CSII or multiple daily injections)
- HbA1C<8.0%
- Ability to give written informed consent to participate in the study
- BMI between 20-29
Key exclusion criteria (12 listed)
- History of significant cardiac, hepatic, renal or neurological disease.
- Significant head injury, epilepsy or hypoglycaemia-induced seizures.
- Pregnancy.
- Breast feeding mothers.
- Participants on thiazide diuretics
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 |
|---|---|---|
| DiazoxideAlso: Eudemine (Diazoxide)Diazoxide 7mg/kg, given 2 hours before the start of the clamp study | Drug | Diazoxide |
| PlaceboAlso: Lactose Ph capsules (Placebo)Lactose Ph capsules (Placebo) | Drug | Placebo |
Primary outcome
Adrenaline response(pmol/L) at 2.5mmol/L of glucose
Time frame: 1 year
The body secretes hormones such as adrenaline as a response to low blood sugars. Patients who have had insulin-dependant diabetes for over 5 years rely heavily on adrenaline release, to produce symptoms, so that they can respond appropriately to low blood sugars. However, this response is blunted in those with type 1 diabetes. Our question is whether the magnitude of this response can be increased by use of diazoxide in the context of hypoglycaemia, so that patients with insulin-dependant diabetes become better aware of hypoglycaemia.
1 secondary outcome
Glucose Thresholds (calculated when counter-regulatory hormone release is greater than 2SD of hormone level at euglycaemia 4.0mmol/L blood sugar) of each of the counter-regulatory hormones (adrenaline, noradrenalin, glucagon)
Time frame: 1 year
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 14 Oct 2019.
- Background: PubMed 25591873George PS, Tavendale R, Palmer CN, McCrimmon RJ. Diazoxide improves hormonal counterregulatory responses to acute hypoglycemia in long-standing type 1 diabetes. Diabetes. 2015 Jun;64(6):2234-41. doi: 10.2337/db14-1539. Epub 2015 Jan 15.
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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.
Rory J McCrimmon, MD study chair
Clinical Reader
Priya S George, MRCP principal investigator
Clinical Research Fellow
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Diazoxide in people with Type 1 Diabetes, run by University of Dundee 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 5 inclusion and 12 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 14 Oct 2019. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Adrenaline response(pmol/L) at 2.5mmol/L of glucose (time frame: 1 year). 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 NCT01488136, 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 14 Oct 2019; AzTrials last refreshed its copy on 6 Nov 2026.