Use of Diazoxide in Acute Hypoglycaemia
2 other identifiers
interventional
12
1 country
1
Brief 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). 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_4
Started Jan 2012
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 26, 2011
CompletedFirst Posted
Study publicly available on registry
December 8, 2011
CompletedStudy Start
First participant enrolled
January 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2013
CompletedOctober 14, 2019
October 1, 2019
1.2 years
October 26, 2011
October 11, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
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)
1 year
Other Outcomes (1)
Symptom scores and Cognitive function scores at 2.5mmol/L
Done during the hyperinsulinaemic hypoglycaemic clamp
Study Arms (2)
Diazoxide
ACTIVE COMPARATOROral diazoxide 7 mg/kg
Placebo
PLACEBO COMPARATORMatched placebo
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Dundeelead
- Juvenile Diabetes Research Foundationcollaborator
Study Sites (1)
NHS Tayside
Dundee, DD1 9SY, United Kingdom
Related Publications (1)
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.
PMID: 25591873BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Rory J McCrimmon, MD
Clinical Reader
- PRINCIPAL INVESTIGATOR
Priya S George, MRCP
Clinical Research Fellow
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 26, 2011
First Posted
December 8, 2011
Study Start
January 1, 2012
Primary Completion
March 1, 2013
Study Completion
March 1, 2013
Last Updated
October 14, 2019
Record last verified: 2019-10