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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