Type 2 Diabetes MellitusNCT02205996
The Effects of Hypoglycaemia in People With Type 2 Diabetes
A study testing Insulin (Humulin S) and Euglycaemic Hypoglycaemic Insulin clamp in people with Type 2 Diabetes Mellitus, run by University of Hull at 1 site in United Kingdom.
Trial summary
Strict glycaemic control has been associated with increased hypoglycaemia and mortality rate, the cause of which was unclear, in subjects with type 2 diabetes. In this study, we hypothesised that acute hypoglycaemia will result in platelet activation in people with type 2 diabetes to a higher degree than controls. Read more about this study
- Who is it for?
- Ages 40 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Insulin (Humulin S) and Euglycaemic Hypoglycaemic Insulin clamp
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2011to May 2013
- 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 40 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy volunteers:
- Males or females
- On no medications except for the contraceptive pill and without medical illnesses in the last three months.
- Non-smokers
- 40 - 60 years of age.
- T2DM subjects:
Show all 12Show fewer
- Males or females
- Diagnosis of T2DM
- 40 - 60 years of age
- HbA1C: 6.5 - 9.5%
- Duration of diabetes 1 - 10 years
- Diabetes treated with diet, or tablets only.
Who cannot join
- Healthy volunteers:
- Pregnancy
- Lack of contraception in women of child bearing age
- Chronic medical conditions
- Current smokers
- Evidence of ischaemia on ECG
Show all 24Show fewer
- Drop attacks
- Alcohol or drug abuse
- Psychiatric illness
- Previous history of seizure
- Alcohol or drug abuse
- Type 2 diabetes subjects:
- Pregnancy
- Current smokers
- Recurrent episodes of hypoglycaemia
- Treatment with anti-platelet or anti-coagulation therapy
- History of ischaemic heart disease, stroke or peripheral vascular disease
- Epilepsy
- Drop attacks
- Evidence of ischaemia on ECG
- Insulin treated T2DM
- History of microvascular disease (retinopathy, nephropathy or neuropathy).
- Alcohol or drug abuse
- Psychiatric illness
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effects of Hypoglycaemia on Platelets Function and Inflammatory Markers in People With Type 2 Diabetes and Normal Controls.
Strict glycaemic control has been associated with increased hypoglycaemia and mortality rate, the cause of which was unclear, in subjects with type 2 diabetes. In this study, we hypothesised that acute hypoglycaemia will result in platelet activation in people with type 2 diabetes to a higher degree than controls.
Read the detailed description
Type 2 diabetes is associated with increased risk of cardiovascular disease. Although the United Kingdom Prospective Diabetes Study (UKPDS) follow-up data suggested reduced macrovascular complications with tight glycaemic control, recent studies in people with type 2 diabetes failed to replicate these findings. Furthermore, all-cause mortality was found to be increased with strict glycaemic control in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. The cause of the increased deaths remains unclear.
Strict glycaemic control is associated with increased risk of hypoglycaemia. Although, hypoglycaemia has traditionally been considered a complication of the treatment for type 1 diabetes, it has recently been recognised as a problem in people with type 2 diabetes particularly those on insulin therapy. In the ACCORD study, the risk of death was significantly increased in those with one or more episode of severe hypoglycaemia in both the strict and standard study treatment arms. As plasma glucose falls to below 4.0 mmol/L, a series of defence mechanisms occur, at an individualised glycaemic thresholds, to reverse hypoglycaemia including a rise in catecholamine levels. This may lead to hypokalaemia, prolonged QT interval, and cardiac arrhythmias. It may also lead to impaired cardiovascular autonomic function for up to 16 hours afterwards; increased inflammatory markers; platelet activation and promote vascular damage. As the majority of studies assessing the effects of hypoglycaemia on cardiovascular risk markers are conducted in people with type 1 diabetes and healthy controls, their findings may not necessarily be applicable to people with type 2 diabetes. In particular, the effects of hypoglycaemia on platelet function and thrombotic risk in people with type 2 diabetes require further clarification. In this study, we hypothesised that acute hypoglycaemia will result in platelet activation in people with type 2 diabetes to a higher degree than controls.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Insulin (Humulin S), Euglycaemic Hypoglycaemic Insulin clamp
- Keywords
- Type 2 diabetes, Hypoglycaemia, Platelets, Inflammation
- Medical subject headings
- Diabetes Mellitus, Type 2, Hypoglycemia, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin (Humulin S)Drug
Also called Glucose (20% Dextrose).
Using insulin and glucose infusions (hyperinsulinaemic clamps), blood glucose levels were stabilised over 1 hour to reach 5 mmol/L and maintained at that level for 1 hour, then gradually reduced over 1 hour to 2.8 mmol/L and maintained at that level for 1 hour. Blood samples were collected at times 0 (baseline), 2 hours (euglycaemia), 4 hours (hypoglycaemia) and at 24 hours after the clamp studies.
Euglycaemic Hypoglycaemic Insulin clampDevice
| Study group | Role | What they receive |
|---|---|---|
| Controls | Active comparator | Weight-matched healthy controls. Euglycaemic Hypoglycaemic insulin clamp. Using hyperinsulinaemic clamps, blood glucose levels were stabilised over 1 hour to reach 5 mmol/L and maintained at that level for 1 hour, then gradually reduced over 1 hour to 2.8 mmol/L and maintained at that level for 1 hour. Blood samples were collected at times 0 (baseline), 2 hours (euglycaemia), 4 hours (hypoglycaemia) and at 24 hours after the clamp studies. Receives: Drug: Insulin (Humulin S); Device: Euglycaemic Hypoglycaemic Insulin clamp |
| Type 2 diabetes | Active comparator | People with a known diagnosis of type 2 diabetes. Euglycaemic Hypoglycaemic Insulin clamp. Using hyperinsulinaemic clamps, blood glucose levels were stabilised over 1 hour to reach 5 mmol/L and maintained at that level for 1 hour, then gradually reduced over 1 hour to 2.8 mmol/L and maintained at that level for 1 hour. Blood samples were collected at times 0 (baseline), 2 hours (euglycaemia), 4 hours (hypoglycaemia) and at 24 hours after the clamp studies. Receives: Drug: Insulin (Humulin S); Device: Euglycaemic Hypoglycaemic Insulin clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
To examine the effect of hypoglycaemia on platelet surface expression of platelet activation markers P-selectin and fibrinogen binding.
Platelet surface expression of activation markers, P-selectin and fibrinogen binding, were measured in the resting state (unstimulated samples) and in response to stimulation with platelet agonist adenosine diphosphate, and platelet inhibitor prostacyclin.
A change in platelet function from times 0 (baseline), to 2 hours (euglycaemia), 4 hours (hypoglycaemia) and 24 hours after the clamp studies was measured and compared between the two groups.
Measured: Up to 24 hours after euglycaemic hypoglycaemic clamp
Secondary outcomes (1)
To measure changes in markers of inflammation (high sensitivity C-reactive protein) and endothelial function using EndoPat 2000
High sensitivity C-reactive protein was measured at baseline (time 0), 2 hours (euglycaemia), 4 hours (hypoglycaemia) and 24 hours after clamp studies. Changes from baseline were compared between the groups.
EndoPat was measured before the insulin clamp and 24 hours afterwards and changes were compared between the two groups.
Measured: Up to 24h after euglycaemic hypoglycaemic clamp
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2014 (estimated)
- Study startNov 2011
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Hull
- Sponsor type
- University, hospital or other
- Collaborators
- Hull University Teaching Hospitals NHS Trust
- Responsible party
- Principal investigator, Thozhukat Sathyapalan, University of Hull
- Investigators
- Stephen L Atkin, PhD, Principal investigator, University of Hull
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02205996
- Sponsor's protocol ID
- 11/YH/0161
- Status last verified
- Jul 2014
- First submitted
- 28 Jul 2014
- Last updated
- 1 Aug 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Moin ASM, Sathyapalan T, Atkin SL, Butler AE. The severity and duration of Hypoglycemia affect platelet-derived protein responses in Caucasians. Cardiovasc Diabetol. 2022 Oct 6;21(1):202. doi: 10.1186/s12933-022-01639-w.
PubMed 36203210Moin ASM, Nandakumar M, Kahal H, Sathyapalan T, Atkin SL, Butler AE. Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia. Cells. 2021 Nov 10;10(11):3109. doi: 10.3390/cells10113109.
PubMed 34831332Moin ASM, Kahal H, Al-Qaissi A, Kumar N, Sathyapalan T, Atkin SL, Butler AE. Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemia. BMJ Open Diabetes Res Care. 2021 Apr;9(1):e002211. doi: 10.1136/bmjdrc-2021-002211.
PubMed 33931404
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Hypoglycaemia on Platelets Function and Inflammatory Markers in People With Type 2 Diabetes and Normal Controls.
- ClinicalTrials.gov ID
- NCT02205996
- Acronym / sponsor ID
- 11/YH/0161
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Type 2 diabetes, Hypoglycaemia, Platelets, Inflammation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of HullUniversity, hospital or other
- Collaborators
- Hull University Teaching Hospitals NHS Trust
- Study start
- Nov 2011
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 1 Aug 2014 (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.
Strict glycaemic control has been associated with increased hypoglycaemia and mortality rate, the cause of which was unclear, in subjects with type 2 diabetes. In this study, we hypothesised that acute hypoglycaemia will result in platelet activation in people with type 2 diabetes to a higher degree than controls.
Detailed description
Type 2 diabetes is associated with increased risk of cardiovascular disease. Although the United Kingdom Prospective Diabetes Study (UKPDS) follow-up data suggested reduced macrovascular complications with tight glycaemic control, recent studies in people with type 2 diabetes failed to replicate these findings. Furthermore, all-cause mortality was found to be increased with strict glycaemic control in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. The cause of the increased deaths remains unclear.
Strict glycaemic control is associated with increased risk of hypoglycaemia. Although, hypoglycaemia has traditionally been considered a complication of the treatment for type 1 diabetes, it has recently been recognised as a problem in people with type 2 diabetes particularly those on insulin therapy. In the ACCORD study, the risk of death was significantly increased in those with one or more episode of severe hypoglycaemia in both the strict and standard study treatment arms. As plasma glucose falls to below 4.0 mmol/L, a series of defence mechanisms occur, at an individualised glycaemic thresholds, to reverse hypoglycaemia including a rise in catecholamine levels. This may lead to hypokalaemia, prolonged QT interval, and cardiac arrhythmias. It may also lead to impaired cardiovascular autonomic function for up to 16 hours afterwards; increased inflammatory markers; platelet activation and promote vascular damage. As the majority of studies assessing the effects of hypoglycaemia on cardiovascular risk markers are conducted in people with type 1 diabetes and healthy controls, their findings may not necessarily be applicable to people with type 2 diabetes. In particular, the effects of hypoglycaemia on platelet function and thrombotic risk in people with type 2 diabetes require further clarification. In this study, we hypothesised that acute hypoglycaemia will result in platelet activation in people with type 2 diabetes to a higher degree than controls.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Controls | Active comparator | Drug: Insulin (Humulin S), Device: Euglycaemic Hypoglycaemic Insulin clampWeight-matched healthy controls. Euglycaemic Hypoglycaemic insulin clamp. Using hyperinsulinaemic clamps, blood glucose levels were stabilised over 1 hour to reach 5 mmol/L and maintained at that level for 1 hour, then gradually reduced over 1 hour to 2.8 mmol/L and maintained at that level for 1 hour. Blood samples were collected at times 0 (baseline), 2 hours (euglycaemia), 4 hours (hypoglycaemia) and at 24 hours after the clamp studies. |
| Type 2 diabetes | Active comparator | Drug: Insulin (Humulin S), Device: Euglycaemic Hypoglycaemic Insulin clampPeople with a known diagnosis of type 2 diabetes. Euglycaemic Hypoglycaemic Insulin clamp. Using hyperinsulinaemic clamps, blood glucose levels were stabilised over 1 hour to reach 5 mmol/L and maintained at that level for 1 hour, then gradually reduced over 1 hour to 2.8 mmol/L and maintained at that level for 1 hour. Blood samples were collected at times 0 (baseline), 2 hours (euglycaemia), 4 hours (hypoglycaemia) and at 24 hours after the clamp studies. |
Who may qualify
- Ages
- 40 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Healthy volunteers:
- T2DM subjects:
Key exclusion criteria (24 listed)
- Healthy volunteers:
- Type 2 diabetes subjects:
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 |
|---|---|---|
| Insulin (Humulin S)Also: Glucose (20% Dextrose).Using insulin and glucose infusions (hyperinsulinaemic clamps), blood glucose levels were stabilised over 1 hour to reach 5 mmol/L and maintained at that level for 1 hour, then gradually reduced over 1 hour to 2.8 mmol/L and maintained at that level for 1 hour. Blood samples were collected at times 0 (baseline), 2 hours (euglycaemia), 4 hours (hypoglycaemia) and at 24 hours after the clamp studies. | Drug | Controls, Type 2 diabetes |
| Euglycaemic Hypoglycaemic Insulin clamp | Device | Controls, Type 2 diabetes |
Primary outcome
To examine the effect of hypoglycaemia on platelet surface expression of platelet activation markers P-selectin and fibrinogen binding.
Time frame: Up to 24 hours after euglycaemic hypoglycaemic clamp
Platelet surface expression of activation markers, P-selectin and fibrinogen binding, were measured in the resting state (unstimulated samples) and in response to stimulation with platelet agonist adenosine diphosphate, and platelet inhibitor prostacyclin. A change in platelet function from times 0 (baseline), to 2 hours (euglycaemia), 4 hours (hypoglycaemia) and 24 hours after the clamp studies was measured and compared between the two groups.
1 secondary outcome
To measure changes in markers of inflammation (high sensitivity C-reactive protein) and endothelial function using EndoPat 2000
Time frame: Up to 24h after euglycaemic hypoglycaemic clamp
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 1 Aug 2014.
- Derived from this study: PubMed 36203210Moin ASM, Sathyapalan T, Atkin SL, Butler AE. The severity and duration of Hypoglycemia affect platelet-derived protein responses in Caucasians. Cardiovasc Diabetol. 2022 Oct 6;21(1):202. doi: 10.1186/s12933-022-01639-w.
- Derived from this study: PubMed 34831332Moin ASM, Nandakumar M, Kahal H, Sathyapalan T, Atkin SL, Butler AE. Heat Shock-Related Protein Responses and Inflammatory Protein Changes Are Associated with Mild Prolonged Hypoglycemia. Cells. 2021 Nov 10;10(11):3109. doi: 10.3390/cells10113109.
- Derived from this study: PubMed 33931404Moin ASM, Kahal H, Al-Qaissi A, Kumar N, Sathyapalan T, Atkin SL, Butler AE. Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemia. BMJ Open Diabetes Res Care. 2021 Apr;9(1):e002211. doi: 10.1136/bmjdrc-2021-002211.
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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.
Stephen L Atkin, PhD principal investigator
University of Hull
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Insulin (Humulin S) and Euglycaemic Hypoglycaemic Insulin clamp in people with Type 2 Diabetes Mellitus, run by University of Hull 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 12 inclusion and 24 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 1 Aug 2014. 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?
To examine the effect of hypoglycaemia on platelet surface expression of platelet activation markers P-selectin and fibrinogen binding. (time frame: Up to 24 hours after euglycaemic hypoglycaemic clamp). 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 NCT02205996, which also lists 3 linked publications.
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 1 Aug 2014.