NCT02205996

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at below P25 for not_applicable type-2-diabetes-mellitus

Timeline
Completed

Started Nov 2011

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2011

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2013

Completed
1.2 years until next milestone

First Submitted

Initial submission to the registry

July 28, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 1, 2014

Completed
Last Updated

August 1, 2014

Status Verified

July 1, 2014

Enrollment Period

1.5 years

First QC Date

July 28, 2014

Last Update Submit

July 31, 2014

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 diabetesHypoglycaemiaPlateletsInflammation

Outcome Measures

Primary Outcomes (1)

  • 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.

    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

    Up to 24h after euglycaemic hypoglycaemic clamp

Other Outcomes (1)

  • To assess the effects of hypoglycaemia on participants scores on cognitive function tests

    Up to 24h after euglycaemic hypoglycaemic clamp

Study Arms (2)

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.

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.

Drug: Insulin (Humulin S)Device: Euglycaemic Hypoglycaemic Insulin clamp

Interventions

Insulin (Humulin S)DRUG

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.

Also known as: Glucose (20% Dextrose).
ControlsType 2 diabetes
Euglycaemic Hypoglycaemic Insulin clampDEVICE
ControlsType 2 diabetes

Eligibility Criteria

Age40 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy volunteers:
  • Males or females
  • On no medications except for the contraceptive pill and without medical illnesses in the last three months.
  • Non-smokers
  • years of age.
  • T2DM subjects:
  • Males or females
  • Diagnosis of T2DM
  • years of age
  • HbA1C: 6.5 - 9.5%
  • Duration of diabetes 1 - 10 years
  • Diabetes treated with diet, or tablets only.

You may not qualify if:

  • Healthy volunteers:
  • Pregnancy
  • Lack of contraception in women of child bearing age
  • Chronic medical conditions
  • Current smokers
  • Evidence of ischaemia on ECG
  • 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
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hull Royal Infirmary

Hull, HU3 2RW, United Kingdom

Location

Related Publications (3)

  • 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.

    PMID: 36203210DERIVED

  • Moin 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.

    PMID: 34831332DERIVED

  • Moin 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.

    PMID: 33931404DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2HypoglycemiaInflammation

Interventions

InsulinInsulin, Regular, HumanGlucose

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

ProinsulinInsulinsPancreatic HormonesPeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsPeptidesAmino Acids, Peptides, and ProteinsHexosesMonosaccharidesSugarsCarbohydrates

Study Officials

  • Stephen L Atkin, PhD

    Hull York Medical School

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Dr

Study Record Dates

First Submitted

July 28, 2014

First Posted

August 1, 2014

Study Start

November 1, 2011

Primary Completion

May 1, 2013

Study Completion

May 1, 2013

Last Updated

August 1, 2014

Record last verified: 2014-07

Locations

GB(1)