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Prevention of Severe Hypoglycaemia With Hypo-Safe Hypoglycaemia Alarm Device

Primary Purpose

Type 1 Diabetes

Status
Withdrawn
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Hyposafe Hypoglycaemia alarm device
Sponsored by
UNEEG Medical A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Type 1 Diabetes

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male and female patient with type 1 diabetes for at least one year
  • Age 18-70 years
  • Impaired awareness of hypoglycaemia as defined by

    • A score of ≥4 on the Gold-scale (Appendix 8) or
    • Two or more occasions of severe hypoglycaemia (need of help from third person) within the past 12 month
  • Multiple injection insulin therapy or continuous insulin injection therapy
  • For female participants: Not pregnant and, if child bearing potential, usage of reliable anti-contraceptive method during the study period

Exclusion Criteria:

  • Severe cardiac disease

    • History of myocardial infarction
    • Cardiac arrhythmia
  • Previous stroke or cerebral haemorrhage and any other structural cerebral disease
  • Active cancer or cancer diagnosis within the past five years
  • Uremia defined as s-creatinine above 3 times upper reference value
  • Liver disease defined as s-ALAT above 3 times upper reference interval
  • Inability to understand the informed consent
  • Epilepsy
  • Use of antiepileptic drugs for any purposes
  • Clinical important hearing impairment
  • Use of active implantable medical device including

    • Pacemaker and ICD-unit
    • Cochlear implant
  • Use of following drugs

    • Chemotherapeutic drugs of any kind
    • Methotrexate
    • Third generation antipsychotic drugs (aripiprazole, quetiapine, clozapine, ziprasidone, paliperidone, risperidone, sertindole, amisulpride, olanzapine
  • Abuse of alcohol (defined as consumption of > 250g alcohol (in Danish: 21 "genstande") per week or abuse of any other neuroactive substances
  • Infection at the site of device-implantation
  • Any hemorrhagic disease
  • Diving (snorkel diving allowed) or parachute jumping
  • Patients that are judged incapable of understanding the patient information or who are not capable of carrying through the investigation

Sites / Locations

  • Hillerød Sygehus

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Hyposafe Hypoglycemia alarm device

Regular glucose control

Arm Description

EEG based hypoglycemia detection

Regular glucose control group

Outcomes

Primary Outcome Measures

The frequency of severe hypoglycaemia event

Secondary Outcome Measures

The frequency of clinical hypoglycaemia (sensation of hypoglycaemia and BG<3.5mmol/l), biochemical hypoglycaemia (BG<3.5mmol/l), and nocturnal hypoglycaemia (waking up with a sensation of hypoglycaemia and BG<3.5mmol/l)

Full Information

First Posted
November 18, 2009
Last Updated
March 7, 2014
Sponsor
UNEEG Medical A/S
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1. Study Identification

Unique Protocol Identification Number
NCT01178476
Brief Title
Prevention of Severe Hypoglycaemia With Hypo-Safe Hypoglycaemia Alarm Device
Official Title
Prevention of Severe Hypoglycaemia With Hypo-Safe Hypoglycaemia Alarm Device
Study Type
Interventional

2. Study Status

Record Verification Date
August 2010
Overall Recruitment Status
Withdrawn
Study Start Date
November 2009 (undefined)
Primary Completion Date
January 2010 (Anticipated)
Study Completion Date
March 2011 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
UNEEG Medical A/S

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Hypoglycaemia is the most common acute complication in insulin-treated diabetes. The fear of hypoglycaemia discourages diabetic subjects from the attempt to maintain tight glycemic control, which in turn leads to increased diabetes related morbidity and mortality. Neuroglycopenic hypoglycaemia in insulin-treated diabetic patients is associated with characteristic changes in EEG with a decrease in alpha activity and an increase in delta and theta activity. We have recently demonstrated that hypoglycaemia-associated EEG-changes can be recorded from subcutaneously placed electrodes using an automated mathematical algorithm based on non-linear spectral analysis. Experimental findings hold promises that an alarm, given at the time of EEG-changes, can help the patients to avoid severe hypoglycaemia by ingestion of carbohydrate. This is the first larger scale trial testing the clinical applicability of a hypoglycaemia-alarm based on real-time analysis of EEG-signals.
Detailed Description
The near-normalization of glycemic control has become an established treatment goal in diabetes in order to reduce the risk of late complications such as nephropathy, neuropathy, retinopathy and cardiovascular disease (1). However, the frequency of insulin-induced hypoglycaemia increases several-fold during intensified insulin therapy (2;3) and hypoglycaemia is the most common acute complication in insulin-treated diabetes. The fear of hypoglycaemia discourages diabetic subjects from the attempt to maintain tight glycemic control, which in turn leads to increased diabetes related morbidity and mortality (4;5). Symptoms of hypoglycaemia can be classified as autonomic (warning) symptoms caused by the release of catecholamines and neuroglycopenic symptoms caused by the lack of glucose supply to the brain. Symptoms of hypoglycaemia may be compromised at night-time (nocturnal asymptomatic hypoglycaemia) due to impaired glucose counterregulatory response by adrenaline and glucagon. Some 25% of patients with type 1 diabetes suffer from unawareness in various degrees increasing with long diabetes duration and tight glycemic control (4;6;7). Several studies have evaluated the potential use of continuous glucose monitoring system (CGMS) as hypoglycaemia alarms but so far failed to show reduction in the frequency of severe hypoglycaemia (8;9). Although the technology is continuously being improved it is still associated with a number of problems (10). The technique is rather imprecise, particularly in the lower range of glucose measurements, and only about 33% of hypoglycemic events were detected in a larger clinical trial (11). The accuracy of the reading is reduced when rapid changes in blood glucose occur (12). There is a significant and variable delay from the change in blood glucose to the change in the interstitial compartment ranging from 4 - 10 minutes (13) and the catheters are rather costly and must be replaced every 72 hours. The EEG signal reflects the functional state and metabolism of the brain. The brain is almost totally dependent on a continuous supply of glucose, and when the glucose level is lower than the metabolic requirements of the brain, its function deteriorates. Neuroglycopenic hypoglycaemia in insulin-treated diabetic patients is associated with characteristic changes in EEG with a decrease in alpha activity and an increase in delta and theta activity (14-17). These changes are clearly seen at blood glucose ~2.0mmol/l (14;15) preceding the development of severe cognitive dysfunction (18). We have recently demonstrated that hypoglycaemia-associated EEG-changes can be recorded from subcutaneously placed electrodes using an automated mathematical algorithm based on non-linear spectral analysis and that EEG-changes above a predefined threshold can be demonstrated more than 10 minutes before development of severe hypoglycaemia in the majority of the patients (19). We found a very low rate of false alarms and no adverse reactions related to implantation of the electrodes. We have subsequently performed a number of studies with real-time alarms type 1 diabetes patients exposed to insulin induced hypoglycaemia. In these studies the patients were instructed to ingest carbohydrates when he/she heard the alarm sound. In three out of four cases the patients were able to do so, while a fourth patient did not spontaneously ingest the meal although, he was fully conscious and not clinically affect by the hypoglycaemia. These findings hold promises that an alarm, given at the time of EEG-changes, can help the patients to avoid severe hypoglycaemia by ingestion of carbohydrate. For clinical applicability the device should be able to distinguish hypoglycaemia-induced EEG changes from noise, artefacts and physiological variations in the EEG including the low-frequency waves seen during sleep, with high sensitivity and specificity using a mathematical algorithm that classifies the EEG in real-time. There should be a "time-window" between hypoglycaemia-induced EEG changes and severe cognitive impairment. The device should be fully compatible with normal everyday activities. Thus, the device should be small, fully biocompatible and implantable, and the monitoring and processing unit should be small and have sufficient battery power. This is the first larger scale trial testing the clinical applicability of a hypoglycaemia-alarm based on real-time analysis of EEG-signals.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hyposafe Hypoglycemia alarm device
Arm Type
Experimental
Arm Description
EEG based hypoglycemia detection
Arm Title
Regular glucose control
Arm Type
Active Comparator
Arm Description
Regular glucose control group
Intervention Type
Device
Intervention Name(s)
Hyposafe Hypoglycaemia alarm device
Intervention Description
An EEG based hypoglycemia alarm is tested against standard glucose measurement on the risk of severe hypoglycemia
Primary Outcome Measure Information:
Title
The frequency of severe hypoglycaemia event
Time Frame
six months
Secondary Outcome Measure Information:
Title
The frequency of clinical hypoglycaemia (sensation of hypoglycaemia and BG<3.5mmol/l), biochemical hypoglycaemia (BG<3.5mmol/l), and nocturnal hypoglycaemia (waking up with a sensation of hypoglycaemia and BG<3.5mmol/l)
Time Frame
six months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female patient with type 1 diabetes for at least one year Age 18-70 years Impaired awareness of hypoglycaemia as defined by A score of ≥4 on the Gold-scale (Appendix 8) or Two or more occasions of severe hypoglycaemia (need of help from third person) within the past 12 month Multiple injection insulin therapy or continuous insulin injection therapy For female participants: Not pregnant and, if child bearing potential, usage of reliable anti-contraceptive method during the study period Exclusion Criteria: Severe cardiac disease History of myocardial infarction Cardiac arrhythmia Previous stroke or cerebral haemorrhage and any other structural cerebral disease Active cancer or cancer diagnosis within the past five years Uremia defined as s-creatinine above 3 times upper reference value Liver disease defined as s-ALAT above 3 times upper reference interval Inability to understand the informed consent Epilepsy Use of antiepileptic drugs for any purposes Clinical important hearing impairment Use of active implantable medical device including Pacemaker and ICD-unit Cochlear implant Use of following drugs Chemotherapeutic drugs of any kind Methotrexate Third generation antipsychotic drugs (aripiprazole, quetiapine, clozapine, ziprasidone, paliperidone, risperidone, sertindole, amisulpride, olanzapine Abuse of alcohol (defined as consumption of > 250g alcohol (in Danish: 21 "genstande") per week or abuse of any other neuroactive substances Infection at the site of device-implantation Any hemorrhagic disease Diving (snorkel diving allowed) or parachute jumping Patients that are judged incapable of understanding the patient information or who are not capable of carrying through the investigation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Birger Thorsteinsson, MD.
Organizational Affiliation
Medical Department, Hillerød Sygehus
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hillerød Sygehus
City
Hillerød
ZIP/Postal Code
3400
Country
Denmark

12. IPD Sharing Statement

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Prevention of Severe Hypoglycaemia With Hypo-Safe Hypoglycaemia Alarm Device

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