Table 3.
Published clinical trials based on autophagy modulation in neurodegenerative, infectious, and other diseases.
| Study Design/Registry Number | Regimen | Indication/Autophagy Biomarker | Indication/Aims–Results/Status | Reference |
|---|---|---|---|---|
| Phase II R, DB, PC, MC NCT03693781 Eudract n.2017-004459-21 |
Colchicine 0.01 mg/kg/d; 0.005 mg/kg/d Riluzole: 100 mg/d Treatment: 30 wt Follow-up: 24w |
ALS/Quantification of mRNA and protein levels of p62, LC3, TFEB, ATGs, HSPB8, BAG3, BAG1, HSP70 and HSF1 in PBMCs, lymphoblasts and fibroblasts (transcriptome profile) | Efficacy of colchicine on disease progression as measured by ALS Functional Rating Scale - Revised (ALSFRS-R) at baseline and at treatment end. Results are not yet available. | (Mandrioli et al., 2019) |
| Phase II R, DB, PC, MC Eudract n.2016-002399-28 |
Sirolimus 1 mg/m2/d; 2 mg/m2/d |
ALS/mTOR downstream pathway (S6RP phosphorylation) | Efficacy of sirolimus in ALS patients on functional rating scale, survival, forced vital capacity, and quality of life. Results are not yet available. | (Mandrioli et al., 2018) |
| Case report, OL, R N (Test) = 22 N (control) = 20 |
1,000–1,500 mg metformin plus insulin and anti-TB treatment | Diabetes mellitus and tuberculosis/MAP1LC3B | MET has the potential to enhance the bactericidal effect of antituberculosis (sputum smear reversion after 2 months) via autophagy. MAP1LC3B level increased significantly by metformin treatment. | (Novita et al., 2019) |
| Phase IIa, R, PC, double blind NCT03094546 | Spermidine-based nutritional supplementation | Elderly with subjective cognitive decline/LC3 I/II, p62, EP300, proteomics, metabolomics, polyamine levels, metabolomics, proinflammatory biomarkers, and neurotrophin levels | Results are not yet available. | (Wirth et al., 2019) |
| Phase IIB, OL, RCT CTRI/2018/01/011176 |
İsoniazid: 150–300 mg/d Rifampicin. 300–600 mg/d Pyrazinamide: 800–1,600 mg/d Ethambutol: 550–1,100 mg/d Test group: plus metformin 1,000 mg/d |
Newly diagnosed smear positive pulmonary tuberculosis/immunological and autophagy biomarkers (T cell, monocyte and dendritic cell functions ESAT-6/CFP-10, Culture filtrate Protein, estimation of C reactive protein, tumor necrosis factor-alpha and other cytokines). | Autophagy response will be evaluated as a secondary endpoint. Results are not yet available. | (Padmapriyadarsini et al., 2019) |
| Phase IIa, R, PC, double blind NCT02755246 | Spermidine-rich plant extract supplement | Behavioral mnemonic similarity task/not assessed | Memory performance was moderately enhanced and mnemonic discrimination ability improved in the treatment group versus the placebo group/not assessed | (Wirth et al., 2018) |
| Phase IV, R, quadruple-blind N = 10 NCT02058173 |
CQ: 150 mg/d × 8 + 4 w Placebo 8 w |
HCV/HCV genotype, IL28 genetic polymorphism | A significant decrease in HCV-RNA after the treatments (week 8) was observed in all patients in the CQ-group. The IL28 polymorphism was not associated with 5 HCV RNA load in response to CQ. Preliminary evidence that CQ is possibly a safe treatment option for HCV nonresponders | (Peymani et al., 2016) |
R, randomized; DB, double-blind; OL, open label; PC, placebo-controlled; MC, multicenter; N, number of patients; d, day; w, week; m, month.