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Hypoglycaemia Awareness Restoration Programme (HARPdoc)

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ClinicalTrials.gov Identifier: NCT02940873
Recruitment Status : Recruiting
First Posted : October 21, 2016
Last Update Posted : March 1, 2019
Sponsor:
Collaborators:
Juvenile Diabetes Research Foundation
King's College Hospital NHS Trust
Guy's and St Thomas' NHS Foundation Trust
Sheffield Teaching Hospitals NHS Foundation Trust
Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
Joslin Diabetes Center
Information provided by (Responsible Party):
King's College London

Brief Summary:

Insulin treatment for type 1 diabetes inevitably carries risk of hypoglycaemia (low blood sugar) which can be severe enough to cause coma, seizure, even death. Being unable to feel when blood glucose is falling, a condition called impaired awareness of hypoglycaemia (IAH), increases risk of severe hypoglycaemia 6-fold. IAH can be reversed and risk of severe hypoglycaemia reduced when people are taught how to adjust their insulin around their life-styles through structured education but problematic hypoglycaemia may persist. Many people with apparently intractable IAH and recurrent severe hypoglycaemia have thoughts about hypoglycaemia that form barriers to their ability to avoid hypoglycaemia. They cannot benefit from conventional treatments to reduce hypoglycaemia. The investigators developed the Hypoglycaemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycaemia despite otherwise optimised self-care (HARPdoc), a novel intervention that combines revision of knowledge about hypoglycaemia avoidance with psychological therapies that directly address unhelpful health beliefs about hypoglycaemia. HARPdoc is delivered over six weeks, by diabetes educators to groups of 6 people. In a pilot study, severe hypoglycaemia was greatly reduced in 23 people with very longstanding IAH and recurrent severe hypoglycaemia.

The investigators propose a group-randomised controlled trial of HARPdoc, comparing it to an established educational intervention (Blood Glucose Awareness Training, BGAT) which has also been shown to reduce severe hypoglycaemia. 96 people with type 1 diabetes and problematic hypoglycaemia persisting despite otherwise optimised insulin self-management will be recruited into groups which will be randomised to receive either HARPdoc or BGAT, in 4 centres. The investigators will measure severe hypoglycaemia over two years following courses; hypoglycaemia risk and experience; overall diabetes control and quality of life.


Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Hypoglycemia Behavioral: HARPdoc courses Behavioral: BGAT courses Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Beyond Education: A Hypoglycaemia Awareness Restoration Programme for People With Type 1 Diabetes and Problematic Hypoglycaemia Persisting Despite Optimised Self-care (HARPdoc)
Actual Study Start Date : March 9, 2017
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: HARPdoc courses
Hypoglycaemia Awareness Restoration Programme for adults with type 1 diabetes and problematic hypoglycaemia persisting despite optimised self-care (HARPdoc) - a combination of structured education around hypoglycaemia recognition, avoidance and treatment combined with hypoglycaemia-focussed cognitive behavioural therapy, delivered by diabetes educators, supported by a clinical psychologist, to small groups of eligible adults.
Behavioral: HARPdoc courses
A six week group education package including hypoglycaemia-focussed cognitive behavioural therapy
Other Name: Education and cognitive behavioural therapy

Active Comparator: BGAT courses
Blood Glucose Awareness Training is an existing psycho-educational program which coaches adults with type 1 diabetes better to predict and recognise extremes of plasma glucose - hyper- and hypo-glycaemia. It has been shown to reduce severe hypoglycaemia rates.
Behavioral: BGAT courses
A structured psycho-education programme focussing on better prediction and recognition of high and low blood glucose values
Other Name: Education




Primary Outcome Measures :
  1. Difference in severe hypoglycaemia between study arms [ Time Frame: 12/24 months after randomisation ]
    Difference in rate of severe hypoglycaemia events (number of events over preceding year), adjusted for baseline between the 2 arms at 12 and/or 24 months.


Secondary Outcome Measures :
  1. Difference in rate of moderate hypoglycaemia between study arms [ Time Frame: 12/24 months after randomisation ]
    Difference between moderate hypoglycaemia episodes, defined as any episode of low plasma glucose which was self-treated but where the hypoglycaemia caused significant interruption of current activity, such as having caused impaired performance or embarrassment or having woken the person during sleep, ideally but not necessarily confirmed by a plasma glucose measurement.

  2. The impact on hypoglycaemia without sacrificing diabetes control as reflected by the HbA1c [ Time Frame: 12/24 months after randomisation ]
    The ability to impact on hypoglycaemia without sacrificing diabetes control as reflected by the HbA1c; using a change in HbA1c ≤0.3%, as a measure of lack of change in overall diabetes control between the study arms

  3. Changes in HbA1c > 0.3% and % participants with HbA1c <7%. between study arms [ Time Frame: 12/24 months after randomisation ]
    Changes in HbA1c > 0.3% and % participants with HbA1c <7%. between study arms

  4. Difference in the Gold score between study arms [ Time Frame: 12/24 months after randomisation ]
    The Gold score, in which people rank their awareness of hypoglycaemia from 1 (I am always aware) to 7 (I am never aware), will be used to measure improvement in hypoglycaemia awareness, in terms of both mean scores and number of people regaining awareness by achieving Gold score of less than 4

  5. Difference in awareness of hypoglycaemia by modified Clarke score between study arms [ Time Frame: 12/24 months after randomisation ]
    A modified Clarke score, derived from an 8-item questionnaire which includes a measure of SH frequency, will also be used to measure improvement in hypoglycaemia awareness, in terms of both mean scores and number of people regaining awareness by scoring less than 4. This is a more complex questionnaire

  6. Changes in cognitions around hypoglycaemia using the Attitudes to Awareness between study arms [ Time Frame: 12/24 months after randomisation ]
    The Attitudes to Awareness (A2A) questionnaire to measure change in beliefs and cognitions around hypoglycaemia described by people with IAH that are unhelpful.

  7. Changes in cognitions using the Hypoglycaemia Fear Survey between study arms [ Time Frame: 12/24 months after randomisation ]
    The Hypoglycaemia Fear Survey II, to measure changes in behaviour and worry regarding hypoglycaemia treatment and avoidance

  8. Changes in cognitions around hypoglycaemia using the Hyperglycaemia Avoidance between study arms [ Time Frame: 12/24 months after randomisation ]
    The Hyperglycaemia Avoidance Survey (66) to measure behaviours and worries around hyperglycaemia

  9. Change in psychological health - anxiety and depression using HADS [ Time Frame: 12/24 months after randomisation ]
    Differences from baseline in total, anxiety and depression scores on HADS questionnaire in each study group

  10. Change in psychological health - problems related to diabetes (PAID) [ Time Frame: 12/24 months after randomisation ]
    Differences in PAID scores from baseline in each study group

  11. Quality of Life - general [ Time Frame: 12 months after courses ]
    Scores on questionnaires Short Form 12 (SF-12) in each study group


Other Outcome Measures:
  1. Change in Quality of Life - diabetes specific (DSQoL) [ Time Frame: 12/24 months after randomisation ]
    Change in QOL-Q score in each study group

  2. Difference in exposure to plasma glucose [ Time Frame: 12/24 months following randomisation ]
    Exposure to plasma glucose readings of under 3.9 mmol/l; under 3 mmol/l and under 2.2 exposure to hypoglycaemia alerts, plasma glucose readings of under 3.9 mmol/l event rate (number of events per person per week) and percent of all readings made per patient per week on home glucose monitoring records (downloaded self-monitored finger prick glucoses or of retrospective intermittently monitored "Flash" CGM glucose readings).

  3. Difference in exposure to plasma glucose [ Time Frame: 12/24 months following randomisation ]
    Exposure to hypoglycaemia of both under 3 mmol/l and under 2.2 mmol/l as event rate (number of events per person per week) and percent of all readings made per patient per week on home glucose monitoring records (downloaded self-monitored finger prick glucoses or of retrospective intermittently monitored "Flash" CGM glucose readings)

  4. Difference in exposure to hypoglycaemia alerts [ Time Frame: 12 months following randomisation ]
    Exposure to hypoglycaemia alerts, plasma glucose readings of under 3.9 mmol/l event rate (number of events of at least 15 min duration per person per week) and duration (total time spent at these values in hours and minutes per week) from CGM readings (CGM substudy)

  5. Difference in exposure to plasma glucose [ Time Frame: 12 months following randomisation ]
    Exposure to hypoglycaemia of both under 3 mmol/l and under 2.2 mmol/l as event rate (number of events of at least 15 min duration per person per week) and duration (total time spent at these values in hours and minutes per week) from CGM readings (CGM substudy)

  6. Quality of life for economic assessment EQ-5D [ Time Frame: 12/24 months ]
    EQ-5D score in each group

  7. Difference around hypoglycaemia using the Hypoglycaemia Cues Questionnaire [ Time Frame: 12/24 months ]
    Scores on Hypoglycaemia Cues Questionnaire

  8. Changes in treatment modality [ Time Frame: 12/24 months ]
    We will also document any changes in treatment modality (e.g. new uptake of pumps and/or sensors)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

96 people, of whom 24 will be recruited in the US centre under their ethical regulations.

  • 18 years or older
  • type 1 diabetes(1) for at least four years,
  • Experiencing problematic hypoglycaemia(2) for at least one year, despite structured education(3) in flexible insulin therapy and on-going optimal conventional care.
  • Current use of an appropriate (in the investigator's estimation) multiple daily insulin injection regimen or CSII (insulin pump) therapy(4)
  • Willingness to comply with study design, including willingness and ability to perform SMBG up to 4 times a day routinely
  • Ability to communicate in written and spoken English
  • Ability to give written informed consent.

    1. Type 1 diabetes will be defined clinically, usually based on starting insulin for diabetes within one year of diagnosis and/or a history of diabetic ketoacidosis
    2. Having Gold and Clarke scores of 4 or more and having had ≥ 1 episode/s of severe hypoglycaemia [events requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective action, because of impaired cognitive function, and which may include episodes that were not treated by another but included loss of consciousness or seizure] in the last 2 years and at least one since starting current treatment modality.
    3. Structured education requires a programme with a curriculum, taught by trained educators, which covers insulin dose adjustment around carbohydrate counting and lifestyle issues, and a physiological 24 hr basal insulin replacement separate from meal insulin replacement) or as judged equivalent by the local investigator.
    4. Participant should be using dose adjustment around carbohydrate counting and lifestyle issues, and an appropriate, separate basal replacement)

Exclusion criteria:

  • People with type 2 diabetes, or type 1 diabetes and good hypoglycaemia awareness
  • People with type 1 diabetes and impaired hypoglycaemia awareness who have not attended structured education in flexible intensive insulin therapy, such as DAFNE, BERTIE, the Joslin course (DO IT) or as judged equivalent by the local investigator.
  • People not fluent in spoken English
  • Current pregnancy (5)
  • People with severe mental disorders (schizophrenia, manic depression, depressive psychosis, active suicidal ideation, learning disability, dementia, alcohol and substance dependence, personality disorders, eating disorder)(6).
  • Cognitive impairment independent of hypoglycaemia (e.g. clinical diagnosis of dementia(7), advanced Parkinson's disease, neurodegenerative disease)
  • Existence of co-morbid medical disease other than diabetes mellitus contributing to hypoglycaemia (e.g. inadequately treated Addison's disease or growth hormone deficiency or hypothyroidism; untreated coeliac disease; uncontrolled gastroparesis; end stage renal disease), which must have been checked since the onset of problematic hypoglycaemia.

    (5) Participants who continue to experience severe hypoglycaemia episodes 6 months after they have stopped breastfeeding may be included in the trial.

    (6) "Manic depression" covers conditions such as bi-polar disorder. Pre-existing depression that is on-going but, in the opinion of the investigator, stable and not a barrier to potential benefit from BGAT or HAPRdoc is not an exclusion criterion. Exclusion of individuals with a personality disorder includes those with current or previous clinical diagnosis AND current or previous mental health care for that disorder

    (7) Dementia would cover either an existing diagnosis or a Mini Mental State Examination [MMSE]) score of less than 24.

Participants who have expressed interest in the study, have consented, and have impaired awareness of hypoglycaemia but do not otherwise meet the inclusion criteria due to low number of SH episodes may be included in the HARPdoc educational course as 'fillers' if space is available. These patients will not be randomised, nor entered into the study database. However, they may be asked to complete the open baseline, 12 and 24-month data collection if they agree to do so.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02940873


Contacts
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Contact: Stephanie A Amiel, MB, MD, FRCP 0044 207848 5639 HARPdoc@kcl.ac.uk
Contact: Mustabshira A Qayyum 02078485661 HARPdoc@kcl.ac.uk

Locations
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United States, Massachusetts
Joslin Diabetes Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Astrid Atakov Castillo    617-309-1997    astrid.atakov-castillo@joslin.harvard.edu   
Contact: Elena Toschi       elena.toschi@joslin.harvard.edu   
United Kingdom
Royal Bournemouth Hospital Recruiting
Bournemouth, United Kingdom
Contact: Augustin Brooks       Augustin.brooks@rbch.nhs.uk   
King's College Hospital NHS Foundation Trust and Guy's and St Thomas' NHS Foundation Trust Recruiting
London, United Kingdom
Contact: Mustabshira A Qayyum    02078485661    HARPdoc@kcl.ac.uk   
Sheffield Teaching Hospitals NHS Foundation Trust Recruiting
Sheffield, United Kingdom
Contact: Simon Heller       s.heller@sheffield.ac.uk   
Contact: Chloe Husband       Chloe.Husband@sth.nhs.uk   
Sponsors and Collaborators
King's College London
Juvenile Diabetes Research Foundation
King's College Hospital NHS Trust
Guy's and St Thomas' NHS Foundation Trust
Sheffield Teaching Hospitals NHS Foundation Trust
Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
Joslin Diabetes Center
Investigators
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Principal Investigator: Stephanie A Amiel, MB, MD, FRCP King's College London

Publications of Results:
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Responsible Party: King's College London
ClinicalTrials.gov Identifier: NCT02940873     History of Changes
Other Study ID Numbers: 4-SRA-2017-266-M-N
First Posted: October 21, 2016    Key Record Dates
Last Update Posted: March 1, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by King's College London:
severe hypoglycemia
impaired awareness of hypoglycemia
type 1 diabetes mellitus
cognitive behavioral therapy
structured education

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases