title: Quality of life and objective measures of diabetic neuropathy in a prospective placebo-controlled trial of ruboxistaurin and topiramate.
abstract: BACKGROUND
  The Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN) is a validated comprehensive questionnaire designed to capture the entire spectrum of DN related to large fiber, small fiber, and autonomic neuropathy not captured in existing instruments. We aimed to determine if the Norfolk QOL-DN could be used to capture changes in QOL that correlate with nerve fiber-specific objective measures in a placebo-controlled trial of two agents that affect different nerve fibers.
  
  
  METHODS
  Sixty patients with DN were allocated to treatment on ruboxistaurin (RBX) (n = 18), topiramate (TPX) (n = 18), or placebo (n = 18). QOL-DN was administered and objective measures of nerve function were performed at entry and end of the study period.
  
  
  RESULTS
  Total QOL scores improved significantly in the active treatment groups (RBX -9.56 ± 4.13; TPX -12.22 ± 2.76) but not in placebo (-5.56 ± 3.49). There were differences in nerve function improvement between treatments. Neurological symptom scores (NSS) improved with TPX from 5.5 (2.3) to 4.3 (0.65) (p = .007), sensory scores improved with TPX from 15.5 (1.79) to 8.3 (1.19) (p < .001), motor scores did not change, and sensory and motor impairment scores improved with TPX from 18.8 (2.15) to 12.1 (1.71) (p = .003). Total neuropathy scores (TNS) improved with TPX from 24.35 (2.61) to 16.35 (2.02) (p = .001). Neuropathy total symptom score-6 (NTSS-6) changes were significant for both treatments: RBX 4.38 (0.75) to 1.49 (0.38) (p < .001) and TPX 7.57 (1.3) to 4.26 (0.95) (p = .036). Changes in QOL-DN large fiber subscores correlated (Spearman's rank) significantly with changes in NTSS-6 (r = 0.55; p < .0001), NSS (r = 0.31; p < .04), neuropathy impairment score (NIS) (r = 0.35; p < .02), and TNS (r = 0.48; p < .0006). Changes in QOL-DN small fiber subscores correlated significantly with changes in NTSS-6 total scores (r = 0.40; p < .005) and intraepidermal nerve fiber density (IENFD) (r = -0.29; p < .05).
  
  
  CONCLUSIONS
  Ruboxistaurin produced significant improvement in large fiber measures while TPX produced significant changes in small fiber measures. The Norfolk QOL-DN tool differentiated between these changes captured in the fiber-specific domains. Correlations were found between objective measures of neuropathy and total QOL, but those with nerve fiber domain scores were modest and reinforce the need to quantify QOL as an endpoint in neuropathy independent of other measures.
authors: Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, Virginia, USA. boydal@evms.edu
authors: Amanda
authors: A
authors: Boyd
authors: Carolina
authors: C
authors: Casselini
authors: Etta
authors: E
authors: Vinik
authors: Aaron
authors: A
authors: Vinik
mesh_terms: D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000494:pharmacology; D048909:Diabetes Complications / Q000175:diagnosis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D003929:Diabetic Neuropathies / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008301:Maleimides / Q000494:pharmacology*; D008875:Middle Aged; D010919:Placebos; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011788:Quality of Life; D012107:Research Design; D011795:Surveys and Questionnaires; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D007211:Indoles; D008301:Maleimides; D010919:Placebos; D047428:Protein Kinase Inhibitors; D000077236:Topiramate; D005632:Fructose; C099154:ruboxistaurin