Table 2.
Summary of the different host directed therapeutic drugs in clinical trialsfor the treatment of tuberculosis *.
| S No | Trial ID | Host Directed Therapeutic Drugs | HDT Drug Doseage (mg) | HDT Treatment Duration | Anti-Tuberculosis Drugs (ATD) (Dose) | Study Title | Phase | No. of Participants | Ages Eligible for Study | Study Sponsor | Country | Status | Remarks/Findings |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | CTRI/2018/01/011176 | Metformin | 1000 mg | Given daily for the first 2 months together with ATD followed by another 4 months with only ATD | Rifampicin, isoniazid, ethambuthol and pyrazinamide (Standard doseage) | Evaluation of metformin in combination with rifampicin containing antituberculosis therapy in patients with new, smear-positive pulmonary tuberculosis (METRIF) | 2 | 316 | 18–60 Years | National Institute for Research in Tuberculosis | India | Active | Not applicable |
| 2 | NCT 03891901 | Imatinib | 50 mg, 100 mg, 200 mg and 400 mg | Daily for 14 days followed by another 14 days together with ATD | Isoniazid (300 mg) and rifabutin (300 mg) | A Clinical Trial of the Safety, Pharmacokinetics and Hematologic Effects of Imatinib on Myelopoiesis in Adults When Given With and Without Isoniazid and Rifabutin (IMPACT-TB) | 2 | 72 | 18 to 55 Years | National Institute of Allergy and Infectious Diseases (NIAID) | United States, georgia | Recruiting | Not applicable |
| 3 | NCT 04721795 | Atorvastatin | 30–40 mg | Daily for 2 months together with ATD followed by another 4 months with only ATD | Rifampicin, isoniazid, ethambuthol and pyrazinamide (Standard doseage) | Treating Tuberculosis With the Lipid Lowering Drug Atorvastatin in Nigeria (ATORvastatin in Pulmonary TUBerculosis) (ATORTUB) | 2 | 150 | 18 to 65 Years | Obafemi Awolowo University Teaching Hospital | |||
| 4 | NCT 04504851 | Rosuvastatin | 10 mg | Daily for 2 months together with ATD followed by another 4 months with only ATD | Rifampicin (10 mg/Kg), isoniazid (5 mg/Kg), ethambuthol (25 mg/Kg) and pyrazinamide (15 mg/Kg) | Rosuvastatin Evaluation as a Tuberculosis Treatment Adjunct (ROSETTA) | 2 | 154 | 18 to 75 Years | National University Hospital, Singapore | Philippines, Singapore, Uganda and Vietnam | Not yet recruiting | Not applicable |
| 5 | NCT 03882177 | Pravastatin | 40 mg, 80 mg, 120 mg and 160 mg | Given alone on 1st day followed by another 14 days together with ATD | Rifampicin, isoniazid, ethambuthol and pyrazinamide (Standard doseage) | StAT-TB (Statin Adjunctive Therapy for TB): A Phase 2b Dose-finding Study of Pravastatin in Adults With Tuberculosis | 2 | 35 | 18 Years and older | National Institute of Allergy and Infectious Diseases (NIAID) | South Africa | Active, not recruiting | Not applicable |
| 6 | NCT 02968927 | Everolimus | 0.5 mg | Daily for 112 days together with ATD followed by another 68 days with only ATD | Rifabutin (Standard doseage) | A Ph2 Randomized Trial to Evaluate the Safety Preliminary Efficacy and Biomarker Response of Host Directed Therapies Added to Rifabutin-modified Standard Therapy in Adults With Drug-Sensitive Smear-Positive Pulmonary TB | 2 | 200 | 18 to 65 Years | The Aurum Institute NPC | South Africa | Active, not recruiting | Everolimus in adults as adjunctive therapy for tuberculosis was safe and also improved recovery [154] |
| 7 | NCT 00918086 | Vitamin D | 1.25 mg | Three times a week for a total of 8 weeks followed by another 8 weeks with the same dose given every other week as dietary supplement | Standard ATDs | Impact of Vitamin D Supplementation on Host Immunity to Mycobacterium Tuberculosis and Response to Treatment | 2 | 199 | 18 Years and older | Emory University | United States, Georgia | Completed | Vitamin D supplementation failed to improve the rate of sputum Mtb clearance [156] |
| 8 | NCT 01722396 | Vitamin D | 2.5 mg | Given 8 weeks apart at 8, 16 and 24 weeks as dietary supplement together with standard ATD | Standard ATDs | Pharmacogenetics of Vitamin D Supplementation in Tuberculosis | 3 | 62 | 16 Years and older | University of Birmingham | United Kingdom | Completed | Result awaited |
| 9 | NCT 00788320 | Vitamin D | 1.25 mg | Three times a week for a total of 8 weeks as dietary supplement | Standard ATDs | Antimicrobial Peptide LL-37 (Cathelicidin) Production in Active Tuberculosis Disease: Role of Vitamin D Supplementation | NA | 0 | 18 Years and older | Atlanta VA Medical Center | United States, Georgia | Withdrawn (Inadequate enrollment) | Not applicable |
| 10 | NCT 04593524 | Vitamin D | 0.025 mg | 4 weeks | Standard ATDs | The Role of Vitamin D, A, and Beta Carotene in Tuberculosis Patients With Vitamin D Receptor Gene Polymorphism | NA | 48 | 20 to 60 Years | Universitas Sumatera Utara | Indonesia | Completed | Vitamin D supplementation to patients with vitamin D receptor gene polymorphism showed increased sputum conversion rates. |
| 11 | NCT 00507000 | Cholecalciferol (vitamin D) | 1.5 mg | Given weekly for 2 months followed by the same dose per month for the next 4 months as dietary supplement | Standard ATDs | Role of Oral Vitamin D as an Adjunct Therapy in Category I Pulmonary Tuberculosis Along with Assessment of Immunological Parameters. | 3 | 150 | 18 to 60 Years | Indian Council of Medical Research | India | Unknown | Not applicable |
| 12 | NCT 01130311 | cholecalciferol (vitamin D) | 15 mg | Given at week 0 and week 4 as dietary supplement | Standard ATDs | Clinical Trial of Vitamin D Replacement in Patients With Pulmonary Tuberculosis (SUCCINCT) | NA | 259 | 15 Years and older | Aga Khan University | Pakistan | Completed | Vitamin D supplementation showed improved recovery in all TB patients. It also increased host immune activation in vitamin D deficient patients [157] |
| 13 | NCT 01244204 | Vitamin D | 0.020 mg | Daily dose of 800IU of vitamin D | Standard ATDs | Vitamin D Supplementations as Adjunct to Anti-tuberculosis Drugs | NA | 120 | 10 to 18 Years | Harvard School of Public Health | Mongolia | Completed | Vitamin D supplementation resulted in fewer tuberculin skin test conversions [158] |
| 14 | NCT 00677339 | Vitamin D | 1.25 mg | Given once per month as dietary supplement | Standard ATDs | L-arginine and Vitamin D Adjunctive Therapy in Pulmonary Tuberculosis (TB) (AVDAPT) | 3 | 200 | 15 Years and older | Menzies School of Health Research | Indonesia | Completed | Vitamin D supplementation showed no effect on TB outcomes [159] |
| 15 | NCT 01698476 | Vitamin D | 0.125 mg | Given twice daily for 16 weeks as dietary supplement | Standard ATDs | Immune Reconstitution in Tuberculosis Disease Using Antimicrobial Treatment With Vitamin D and Phenylbutyrate | 2 | 390 | 18 to 75 Years | Karolinska Institutet | Ethiopia | Completed | Daily supplementation along with PBA results in reduction of clinical TB symptoms while the intervention had no effect on sputum conversion [160] |
| 16 | NCT 01698476 | 4-phenylbutyrate(PBA) | 500 mg | Given twice daily for 16 weeks | NA | Immune Reconstitution in Tuberculosis Disease Using Antimicrobial Treatment With Vitamin D and Phenylbutyrate | 2 | 390 | 18 to 75 Years | Karolinska Institutet | Ethiopia | Completed | Daily supplementation together with vitamin D results in reduction of clinical TB symptoms while the intervention had no effect on sputum conversion [160] |
| 17 | NCT 02169570 | Vitamin D | 15 mg | Given at week 0, 4 and 12 as dietary supplement together with standard ATD | NA | Effect of Supplementary Vitamin D in Patients With Diabetes Mellitus and Pulmonary Tuberculosis (EVIDENT Study) | 4 | 435 | 30 to 60 Years | Dow University of Health Sciences | Pakistan | Unknown | Not applicable |
| 18 | NCT 01580007 | Vitamin D | 0.125 mg | Given once daily for 2 months | NA | Clinical Trial of Phenylbutyrate and Vitamin D in Tuberculosis (TB) | 2 | 288 | 18 to 60 Years | International Centre for Diarrhoeal Disease Research, Bangladesh | Bangladesh | Completed | Vitamin D supplementation together with standard short-course therapy showed improved clinical recovery and better sputum culture conversion [150,155] |
| 19 | NCT 01580007 | 4-phenylbutyrate(PBA) | 500 mg | Given twice daily for 2 months | NA | Clinical Trial of Phenylbutyrate and Vitamin D in Tuberculosis (TB) | 2 | 288 | 18 to 60 Years | International Centre for Diarrhoeal Disease Research, Bangladesh | Bangladesh | Completed | PBA supplementation together with vitamin D results in improved clinical recovery and better sputum culture conversion [150,155] |
| 20 | NCT 03011580 | Vitamin D3 | 0.240 mg | Given every day for 8 weeks as dietary supplement | NA | Vitamin D3 to Enhance Resolution of Residual Pulmonary Inflammation in Patients Completing Antituberculosis Treatment (ResolveD-TB) | 2 | 15 | 20 Years and older | Queen Mary University of London | United Kingdom | Completed | Result awaited |
| 21 | NCT 01657656 | Vitamin D | 3.5 mg | Given twice a week as dietary supplement together with standard ATD | NA | Vitamin D Supplementations as Adjunct to Anti-Tuberculosis Drugs in Mongolia | NA | 350 | 18 to 80 Years | Harvard School of Public Health | Mongolia | Completed | Vitamin D supplementation had no effect on sputum culture conversion [161] |
| 22 | NCT 01992263 | Vitamin D | 0.015 mg, 0.050 mg and 0.100 mg | Given Daily for 12 months as dietary supplement | NA | A Trial of Vitamin D Supplementation Among Tuberculosis Patients in South India | NA | 200 | 18 to 60 Years | Cornell University | United States and India | Not yet recruiting | Not applicable |
| 23 | NCT 00366470 | Vitamin D | 2.5 mg | Given once every two weeks for 2 Months as dietary supplement together with standard ATD | NA | A Clinical Trial to Study the Effect of the Addition of Vitamin D to Conventional Treatment in New Pulmonary Tuberculosis Patients | 3 | 250 | 18 to 75 years | Peter Daley | India | Completed | Vitamin D supplementation showed no reduction in time to sputum culture conversion [162]. |
| 24 | NCT 02276755 | Cholecalciferol (vitamin D3) | 0.35 mg | Given weekly for 3 years as dietary supplement | NA | Vitamin D in TB Prevention in School Age Children | 3 | 8851 | 6 to 13 Years | Harvard School of Public Health | Mongolia | Completed | Vitamin D supplementation failed to lower risk of tuberculosis infection [163] |
| 25 | NCT 02880982 | Cholecalciferol (vitamin D3) | 0.25 mg | Given weekly for 3 years as dietary supplement | NA | Trial of Vitamin D Supplementation in Cape Town Primary Schoolchildren (ViDiKids) | 3 | 1743 | 6 to 11 Years | Queen Mary University of London | South Africa | Active, not recruiting | Not applicable |
| 26 | NCT 00419068 |
Cholecalciferol (vitamin D3) | 2.5 mg | Given at week 0, 2, 4 and 6 as dietary supplement together with standard ATD | NA | Trial of Adjunctive Vitamin D in Tuberculosis Treatment | 3 | 146 | 18 Years and older | Barts &The London NHS Trust | United Kingdom | Completed | Vitamin D supplementation showed no effect on time to sputum culture conversion in the whole study population. However, participants with the known vitamin D receptor polymorphism showed quicker sputum culture conversion [152] |
| 27 |
NCT 00157066 |
Ergocalciferol (vitamin D) | 2.5 mg | Single dose as supplement | NA | Effects of Vitamin D Supplementation on Antimycobacterial Immunity | NA | 230 | 18 Years and older | Barts & The London NHS Trust | United Kingdom | Completed | Improved in vitro restriction of BCG-lux luminescence was observed. In addition, antigen-stimulated IFN-gamma was not affected [164] |