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A 6-month, randomized, double-masked, placebo-controlled study evaluating the effects of the protein kinase C-beta inhibitor ruboxistaurin on skin microvascular blood flow and other measures of diabetic peripheral neuropathy.
Diabetes Care. 2007 Apr; 30(4):896-902.DC

Abstract

OBJECTIVE

Diabetes leads to protein kinase C (PKC)-beta overactivation and microvascular dysfunction, possibly resulting in disordered skin microvascular blood flow (SkBF) and other changes observed in diabetic peripheral neuropathy (DPN) patients. We investigate the effects of the isoform-selective PKC-beta inhibitor ruboxistaurin mesylate on neurovascular function and other measures of DPN.

RESEARCH DESIGN AND METHODS

Endothelium-dependent and C fiber-mediated SkBF, sensory symptoms, neurological deficits, nerve fiber morphometry, quantitative sensory and autonomic function testing, nerve conduction studies, quality of life (using the Norfolk Quality-of-Life Questionnaire for Diabetic Neuropathy [QOL-DN]), and adverse events were evaluated for 20 placebo- and 20 ruboxistaurin-treated (32 mg/day) DPN patients (aged > or =18 years; with type 1 or type 2 diabetes and A1C < or =11%) during a randomized, double-masked, single-site, 6-month study.

RESULTS

Endothelium-dependent (+78.2%, P < 0.03) and C fiber-mediated (+56.4%, P < 0.03) SkBF at the distal calf increased from baseline to end point. Significant improvements from baseline within the ruboxistaurin group were also observed for the Neuropathy Total Symptom Score-6 (NTSS-6) (3 months -48.3%, P = 0.01; end point -66.0%, P < 0.0006) and the Norfolk QOL-DN symptom subscore and total score (end point -41.2%, P = 0.01, and -41.0, P = 0.04, respectively). Between-group differences in baseline-to-end point change were observed for NTSS-6 total score (placebo -13.1%; ruboxistaurin -66.0%, P < 0.03) and the Norfolk QOL-DN symptom subscore (placebo -4.0%; ruboxistaurin -41.2%, P = 0.041). No significant ruboxistaurin effects were demonstrated for the remaining efficacy measures. Adverse events were consistent with those observed in previous ruboxistaurin studies.

CONCLUSIONS

In this cohort of DPN patients, ruboxistaurin enhanced SkBF at the distal calf, reduced sensory symptoms (NTSS-6), improved measures of Norfolk QOL-DN, and was well tolerated.

Authors+Show Affiliations

Strelitz Diabetes Institutes, Eastern Virginia Medical School, Norfolk, Virginia, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

17392551

Citation

Casellini, Carolina M., et al. "A 6-month, Randomized, Double-masked, Placebo-controlled Study Evaluating the Effects of the Protein Kinase C-beta Inhibitor Ruboxistaurin On Skin Microvascular Blood Flow and Other Measures of Diabetic Peripheral Neuropathy." Diabetes Care, vol. 30, no. 4, 2007, pp. 896-902.
Casellini CM, Barlow PM, Rice AL, et al. A 6-month, randomized, double-masked, placebo-controlled study evaluating the effects of the protein kinase C-beta inhibitor ruboxistaurin on skin microvascular blood flow and other measures of diabetic peripheral neuropathy. Diabetes Care. 2007;30(4):896-902.
Casellini, C. M., Barlow, P. M., Rice, A. L., Casey, M., Simmons, K., Pittenger, G., Bastyr, E. J., Wolka, A. M., & Vinik, A. I. (2007). A 6-month, randomized, double-masked, placebo-controlled study evaluating the effects of the protein kinase C-beta inhibitor ruboxistaurin on skin microvascular blood flow and other measures of diabetic peripheral neuropathy. Diabetes Care, 30(4), 896-902.
Casellini CM, et al. A 6-month, Randomized, Double-masked, Placebo-controlled Study Evaluating the Effects of the Protein Kinase C-beta Inhibitor Ruboxistaurin On Skin Microvascular Blood Flow and Other Measures of Diabetic Peripheral Neuropathy. Diabetes Care. 2007;30(4):896-902. PubMed PMID: 17392551.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A 6-month, randomized, double-masked, placebo-controlled study evaluating the effects of the protein kinase C-beta inhibitor ruboxistaurin on skin microvascular blood flow and other measures of diabetic peripheral neuropathy. AU - Casellini,Carolina M, AU - Barlow,Patricia M, AU - Rice,Amanda L, AU - Casey,Melissa, AU - Simmons,Kathryn, AU - Pittenger,Gary, AU - Bastyr,Edward J,3rd AU - Wolka,Anne M, AU - Vinik,Aaron I, PY - 2007/3/30/pubmed PY - 2007/6/15/medline PY - 2007/3/30/entrez SP - 896 EP - 902 JF - Diabetes care JO - Diabetes Care VL - 30 IS - 4 N2 - OBJECTIVE: Diabetes leads to protein kinase C (PKC)-beta overactivation and microvascular dysfunction, possibly resulting in disordered skin microvascular blood flow (SkBF) and other changes observed in diabetic peripheral neuropathy (DPN) patients. We investigate the effects of the isoform-selective PKC-beta inhibitor ruboxistaurin mesylate on neurovascular function and other measures of DPN. RESEARCH DESIGN AND METHODS: Endothelium-dependent and C fiber-mediated SkBF, sensory symptoms, neurological deficits, nerve fiber morphometry, quantitative sensory and autonomic function testing, nerve conduction studies, quality of life (using the Norfolk Quality-of-Life Questionnaire for Diabetic Neuropathy [QOL-DN]), and adverse events were evaluated for 20 placebo- and 20 ruboxistaurin-treated (32 mg/day) DPN patients (aged > or =18 years; with type 1 or type 2 diabetes and A1C < or =11%) during a randomized, double-masked, single-site, 6-month study. RESULTS: Endothelium-dependent (+78.2%, P < 0.03) and C fiber-mediated (+56.4%, P < 0.03) SkBF at the distal calf increased from baseline to end point. Significant improvements from baseline within the ruboxistaurin group were also observed for the Neuropathy Total Symptom Score-6 (NTSS-6) (3 months -48.3%, P = 0.01; end point -66.0%, P < 0.0006) and the Norfolk QOL-DN symptom subscore and total score (end point -41.2%, P = 0.01, and -41.0, P = 0.04, respectively). Between-group differences in baseline-to-end point change were observed for NTSS-6 total score (placebo -13.1%; ruboxistaurin -66.0%, P < 0.03) and the Norfolk QOL-DN symptom subscore (placebo -4.0%; ruboxistaurin -41.2%, P = 0.041). No significant ruboxistaurin effects were demonstrated for the remaining efficacy measures. Adverse events were consistent with those observed in previous ruboxistaurin studies. CONCLUSIONS: In this cohort of DPN patients, ruboxistaurin enhanced SkBF at the distal calf, reduced sensory symptoms (NTSS-6), improved measures of Norfolk QOL-DN, and was well tolerated. SN - 1935-5548 UR - https://www.unboundmedicine.com/medline/citation/17392551/A_6_month_randomized_double_masked_placebo_controlled_study_evaluating_the_effects_of_the_protein_kinase_C_beta_inhibitor_ruboxistaurin_on_skin_microvascular_blood_flow_and_other_measures_of_diabetic_peripheral_neuropathy_ L2 - http://care.diabetesjournals.org/cgi/pmidlookup?view=long&amp;pmid=17392551 DB - PRIME DP - Unbound Medicine ER -