Low dose linomide in Type I juvenile diabetes of recent onset: a randomised placebo-controlled double blind trial

Abstract

The quinoline-3-carboxamide, linomide, protects non-obese diabetic mice from diabetes. The effects of linomide on insulin needs and beta cell function were studied in recent juvenile Type I diabetes in a double-blind trial. Patients with recent onset diabetes were randomly assigned to treatment with a fixed dose of 2.5 mg linomide (42 patients) or placebo (21 patients) for 1 year, in addition to insulin and diet. Glycated haemoglobin was 10-15% lower at 9 months (p = 0.003) and 12 months (p < 0.05) in the linomide group. The insulin dose was 32-40% smaller in the linomide group at 3 (p < 0.03), 6 (p < 0.02), 9 (p < 0.001) and 12 months (p = 0.01). Insulin doses correlated negatively with C peptide values (p = 0.001-0.002). The trend for higher C peptide values in the linomide group did not reach significance. In a post hoc subgroup analysis performed in 40 patients (25 from the linomide group and 15 from the placebo group) who still had detectable residual beta cell function at entry, linomide was associated with 45-59% higher C peptide value at 6 months (p < 0.05), 9 months (p < 0.05) and 12 months (p < 0.05). The main adverse effects of linomide were mild transitory anaemia (45 vs 10% in the linomide and placebo groups), thrombocytopenia (24 vs 10%), and mild joint discomfort (45 vs 5%) with no clinical signs. In conclusion, low-dose linomide reduced the insulin needs in patients with juvenile Type I diabetes of recent onset and improved beta cell function in patients who still had detectable beta cell function at entry. These results support further clinical and experimental studies to define the effects of linomide in Type I diabetes provided the safety of linomide is reliably established.

Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial

“…Residual insulin secretion facilitates metabolic control and decreases the risk of keto-acidosis [3], and even modest beta cell function, with stimulated C-peptide above 0.2 nmol/l, may reduce long-term complications [4]. Type 1 diabetes is an autoimmune disease [5]; however, most attempts to use immune intervention to preserve residual beta cell function have achieved limited benefits or have been associated with adverse effects [6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Treatment with anti-CD3 monoclonal antibodies appears to be the most promising treatment to date, but several patients treated in this way, as well as with anti-CD20 monoclonal antibodies, have experienced treatment-related adverse events [20,21].…”

Effect of Photopheresis on Lymphocyte Population in Children with Newly Diagnosed Type 1 Diabetes

“…Several studies have reported that physical, psychological, or chemical stress can produce imbalances in the proportions of T-cell subsets, immunoglobulin levels, and lymphocyte reactivity (6,25,32). Since it became evident that type 1 diabetes may be caused by an autoimmune process, several types of immune interventions have been tried, mostly with minor or transient effects (4,15,19,22,27,33). Photopheresis has been claimed to be an effective form of immunomodulation (37), and it has been used with positive results for the treatment of several immunological diseases, such as rheumatoid arthritis (29), systemic lupus erythematosus (21), psoriatic arthritis (34), and cutaneous T-cell lymphoma (7).…”

Behavioral Genetics of the Depression/Cancer Correlation: A Look at the Ras Oncogene Family and the ‘Cerebral Diabetes Paradigm’

“…Third, the p21 by-product has been shown to mimic the action of insulin in humans (Rapoport et al 1996). Linomide, a drug which upregulates p21, has been successfully administered to patients with type I diabetes of recent onset (Rapoport et al 1996;Coutant et al 1998;Gross et al 2001). This drug reduced the insulin needs of these patients.…”