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).

Impaired awareness of hypoglycaemia (IAH) is a major risk for severe hypoglycaemia in insulin treatment of type 1 diabetes (T1D). To explore the hypothesis that unhelpful health beliefs create barriers to regaining awareness, we conducted a multi-centre, randomised, parallel, two-arm trial (ClinicalTrials.gov NCT02940873) in adults with T1D and treatment-resistant IAH and severe hypoglycaemia, with blinded analysis of 12-month recall of severe hypoglycaemia at 12 and/or 24 months the primary outcome. Secondary outcomes included cognitive and emotional measures. Adults with T1D, IAH and severe hypoglycaemia despite structured education in insulin adjustment, +/- diabetes technologies, were randomised to the "Hypoglycaemia Awareness Restoration Programme despite optimised self-care" (HARPdoc, n = 49), a psychoeducation programme uniquely focussing on changing cognitive barriers to avoiding hypoglycaemia, or the evidence-based "Blood Glucose Awareness Training" (BGAT, n = 50), both delivered over six weeks. Median [IQR] severe hypoglycaemia at baseline was 5[2-12] per patient/year, 1[0-5] at 12 months and 0[0-2] at 24 months, with no superiority for HARPdoc (HARPdoc vs BGAT incident rate ratios [95% CI] 1.25[0.51, 3.09], p = 0.62 and 1.26[0.48, 3.35], p = 0.64 respectively), nor for changes in hypoglycaemia awareness scores or fear. Compared to BGAT, HARPdoc significantly reduced endorsement of unhelpful cognitions (Estimated Mean Difference for Attitudes to Awareness scores at 24 months, -2.07 [-3.37,-0.560], p = 0.01) and reduced scores for diabetes distress (-6.70[-12.50,-0.89], p = 0.02); depression (-1.86[-3.30, -0.43], p = 0.01) and anxiety (-1.89[-3.32, -0.47], p = 0.01). Despite positive impact on cognitive barriers around hypoglycaemia avoidance and on diabetes-related and general emotional distress scores, HARPdoc was not more effective than BGAT at reducing severe hypoglycaemia.