Clinical Dilemmas in Diabetes. Группа авторов

study tests the drug abatacept to see if it can delay or prevent progression of early stage T1D (stage 1 or stage 2), and ultimately prevent clinical diagnosis (stage 3). Pathway to Prevention Currently Enrolling This study screens and observes relatives of people with type 1 diabetes to learn more about how the disease occurs

The use of immunosuppressive drugs has also been proposed as a possible approach to decelerate the evolution of the disease.

      In a multicenter, double‐masked, randomized controlled trial, Abatacept (CTLA4‐Ig) has been administered on days 1, 14, 28, and then every 28 days through a 30 min intravenous infusion at a dose of 10 mg/kg [47]. Results from this study showed that Abatacept was more efficient compared to placebo in preserving the β‐cell mass, as evidenced by stimulated C‐peptide secretion. However, the effect diminished with time; therefore, further investigation will be necessary in order to unravel whether the beneficial effect persists after cessation of infusions. Indeed, Abatacept is a potential candidate to be used in tertiary prevention trials, and is a candidate for use in combination therapies for recent‐onset T1D patients.

      GAD65 (the 65 kDa isoform of glutamic acid decarboxylase) is a human enzyme that has an important role in the nervous system and in several nervous system diseases, e.g. Parkinson's disease and chronic pain.

      GAD65 is also found in the insulin producing β‐cells of the pancreas, although its function at this site is not yet fully established. It is however clear that GAD65 is one of the most important targets when the immune system attacks the insulin producing β‐cells in autoimmune diabetes. Thus, treatment with rhGAD65 is thought to induce tolerance to GAD65, thereby intervening in the autoimmune attack and preserving the capacity to produce insulin in patients with autoimmune diabetes.

      Although ongoing studies are investigating whether rhGAD65 can preserve β‐cell function in recently diagnosed individuals with T1D, trials carried out to date do not demonstrate a significant reduction in the loss of stimulated C‐peptide in recently diagnosed children and young adults (10–20 years) with T1D over a 15‐month period [48].

GAD65 was also targeted in NOD mice in order to reduce the number of GAD65‐specific T effector cells [49], achieving normoglycemia in 70% of NOD mice. Based on this findings, antigen‐based immunotherapy therapy with subcutaneous GAD‐alum have been tested to slow down the course of loss of insulin in patients with recently diagnosed T1D. Recently, the prevention trial DIAPREV‐IT has showed that GAD‐Alum as a subcutaneous prime and boost injection was safe in prediabetic young children but did not affect progression to T1D [50]. The beneficial for prevention of T1D of GAD‐alum should be tested in future prevention studies.

TABLE 2.3 Immunotherapy trials that are awaiting, or currently recruiting, participants. (Source: www.clinicaltrials.gov)

ClinicalTrials.gov identifier	Title	Intervention	Primary outcome
NCT02307695	The Effect of Saxagliptin on Glucose Fluctuation and Immune Regulation in Patients with Type 1 Diabetes	Saxagliptin	MAGE at 24 weeks
NCT01559025	Evaluation of Vildagliptin (Galvus®) as add‐on to Insulin in Residual β‐cell Function and Inflammatory Markers in New‐onset Type 1 Diabetes Mellitus	Vildagliptin	MMTT C‐peptide at 3, 6, 9 and 12 month
NCT02442544	Effect of Prebiotic Fibre on Gut Microbiota, Intestinal Permeability and Glycaemic Control in Children with Type 1 Diabetes: A Pilot Randomized, Double Blind, Placebo Controlled Study	Prebiotic 1:1 oligofructose:inulin	HbA1C at 3 months
NCT02820558	A Phase I Study of Safety and Pharmacological Activity of Substance P in the Reversal of Recent‐Onset Type 1 Diabetes	Substance P	Safety at 20–27 days
NCT02505893	A Monocentric, Open‐label Pilot Study to Assess the Safety and Efficacy of Minimal Islet Transplantation in Patients with New‐onset Type 1 Diabetes	ATG + pG‐CSF + rapamycin + human pancreatic islet	Safety and MMTT C‐peptide at 12 months
NCT02940418	Use of Stem Cells in Diabetes Mellitus Type 1	AD‐MSCs + BM‐MNCs	Safety at 6 months
NCT02293837	EXTEND	Tocilizumab	MMTT C‐peptide at 12 months
NCT02617654	A Randomized, Double‐blinded Placebo‐controlled, Paralleled Designed, Investigator Sponsored Study of the Effect of the GLP‐1 Receptor Agonist Liraglutide on Β‐cell Function in C‐peptide Positive Type 1 Diabetic Patients	Liraglutide	MMTT C‐peptide at 12 months
NCT03170544	A Single Ascending Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK‐1092 in Healthy Subjects and in Subjects With Type 1 Diabetes Mellitus	MK‐1092	Safety and maximal glucose infusion rate at 33 days
NCT02814838	A Phase 2, Multicentre, Randomized, Double‐blind, Placebo‐controlled Study in Patients with New‐onset Type 1 Diabetes	Ladarixin	MMTT C‐peptide at 13±1 weeks
NCT02411253	DIABIL‐2	rhIL‐2	MMTT C‐peptide at 12 months
NCT02803892	MONORAPA	Rapamycin /+ Vildagliptin	MMTT C‐peptide at 4±1, 12±2 weeks
NCT02218619	Clinical Investigation of Efficacy of Tauroursodeoxycholic Acid (TUDCA) to Enhance Pancreatic Β‐cell Survival in Type 1 Diabetes by Reducing Endoplasmic Reticulum Stress	Tauroursodeoxycholic Acid (TUDCA)	MMTT C‐peptide at 6, 12, and 18 months
NCT03272269	A Phase I Placebo‐controlled, Double‐blind, Dose Escalation Clinical Trial to Evaluate the Safety and Immune Responses of Imcyse's IMCY‐0098 in Patients With Recent Onset Type 1 Diabetes	IMCY‐0098	Safety at 24 weeks
NCT03032354	Effect of Lactobacillus Rhamnosus GG and Bifidobacterium Lactis BB 12 on Beta‐cell Function in Children With Newly Diagnosed Type 1 Diabetes ‐ a Randomized Controlled Trial	Probiotics	MMTT C‐peptide at 6 and 12 months
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