Hypoglycaemia Awareness Restoration Programme

NCT02940873 | Completed DMC

• 1 other identifier: 4-SRA-2017-266-M-N
• Study Type: interventional
• Target: 99
• Locations: 2 countries
• Sites: 4

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.

Conditions

Type 1 Diabetes Mellitus; Hypoglycemia

Keywords

severe hypoglycemia; impaired awareness of hypoglycemia; type 1 diabetes mellitus; cognitive behavioral therapy; structured education

Outcome Measures

Primary Outcomes (1)

• Difference in severe hypoglycaemia between study arms

  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.

  12/24 months after randomisation

Secondary Outcomes (11)

• Difference in rate of moderate hypoglycaemia between study arms

  12/24 months after randomisation

• The impact on hypoglycaemia without sacrificing diabetes control as reflected by the HbA1c

  12/24 months after randomisation

• Changes in HbA1c > 0.3% and % participants with HbA1c <7%. between study arms

  12/24 months after randomisation

• Difference in the Gold score between study arms

  12/24 months after randomisation

• Difference in awareness of hypoglycaemia by modified Clarke score between study arms

  12/24 months after randomisation

Other Outcomes (8)

• Change in Quality of Life - diabetes specific (DSQoL)

  12/24 months after randomisation

• Difference in exposure to plasma glucose

  12/24 months following randomisation

• Difference in exposure to plasma glucose

  12/24 months following randomisation

Study Arms (2)

HARPdoc courses

EXPERIMENTAL

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

BGAT courses

ACTIVE COMPARATOR

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

Interventions

HARPdoc courses BEHAVIORAL

A six week group education package including hypoglycaemia-focussed cognitive behavioural therapy

Also known as: Education and cognitive behavioural therapy

HARPdoc courses

BGAT courses BEHAVIORAL

A structured psycho-education programme focussing on better prediction and recognition of high and low blood glucose values

Also known as: Education

BGAT courses

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• people, of whom 24 will be recruited in the US centre under their ethical regulations.
• 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.
• 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
• 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.
• 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.
• Participant should be using dose adjustment around carbohydrate counting and lifestyle issues, and an appropriate, separate basal replacement)

You may not qualify if:

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

Sponsors & Collaborators

• King's College London: lead
• Juvenile Diabetes Research Foundation: collaborator
• King's College Hospital NHS Trust: collaborator
• Guy's and St Thomas' NHS Foundation Trust: collaborator
• Sheffield Teaching Hospitals NHS Foundation Trust: collaborator
• Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust: collaborator
• Joslin Diabetes Center: collaborator

Study Sites (4)

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Royal Bournemouth Hospital

Bournemouth, United Kingdom

Location

King's College Hospital NHS Foundation Trust and Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, United Kingdom

Location

Related Publications (4)

• de Zoysa N, Rogers H, Stadler M, Gianfrancesco C, Beveridge S, Britneff E, Choudhary P, Elliott J, Heller S, Amiel SA. A psychoeducational program to restore hypoglycemia awareness: the DAFNE-HART pilot study. Diabetes Care. 2014;37(3):863-6. doi: 10.2337/dc13-1245. Epub 2013 Dec 6.

  PMID: 24319119 RESULT

• Cox DJ, Gonder-Frederick L, Polonsky W, Schlundt D, Kovatchev B, Clarke W. Blood glucose awareness training (BGAT-2): long-term benefits. Diabetes Care. 2001 Apr;24(4):637-42. doi: 10.2337/diacare.24.4.637.

  PMID: 11315822 RESULT

• Amiel SA, Potts L, Goldsmith K, Jacob P, Smith EL, Gonder-Frederick L, Heller S, Toschi E, Brooks A, Kariyawasam D, Choudhary P, Stadler M, Rogers H, Kendall M, Sevdalis N, Bakolis I, de Zoysa N. A parallel randomised controlled trial of the Hypoglycaemia Awareness Restoration Programme for adults with type 1 diabetes and problematic hypoglycaemia despite optimised self-care (HARPdoc). Nat Commun. 2022 Apr 28;13(1):2229. doi: 10.1038/s41467-022-29488-x.

  PMID: 35484106 DERIVED

• Soukup T, Hull L, Smith EL, Healey A, Bakolis I, Amiel SA, Sevdalis N; PWD Group. Effectiveness-implementation hybrid type 2 trial evaluating two psychoeducational programmes for severe hypoglycaemia in type 1 diabetes: implementation study protocol. BMJ Open. 2019 Nov 14;9(11):e030370. doi: 10.1136/bmjopen-2019-030370.

  PMID: 31727650 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia

Interventions

Educational Status; Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Socioeconomic Factors; Population Characteristics; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Stephanie A Amiel, MB, MD, FRCP

  King's College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2016
• First Posted: October 21, 2016
• Study Start: March 9, 2017
• Primary Completion: April 1, 2021
• Study Completion: April 27, 2021
• Last Updated: September 2, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); US (1)