RESUMEN
AIM: Safer and shorter antituberculosis treatment (ATT) regimens represent the unmet medical need. PATIENTS & METHODS: The patients were randomly assigned into two arms: the first (n = 137) received once-daily sublingual honey lozenge formulated with botanical immunomodulator Immunoxel and the second (n = 132) received placebo lozenges along with conventional ATT. Immunoxel and placebo arms were demographically similar: 102 versus 106 had drug-susceptible TB; 28 versus 20 multidrug-resistant TB (MDR-TB); 7 versus 7 extensively drug-resistant TB (XDR-TB); and 22 versus 20 TB-HIV. The primary end point was sputum smear conversion. RESULTS: After 1 month 87 out 132 (65.9%) of Immunoxel recipients became sputum smear negative, whereas 32 out of 127 (25.2%) in placebo group had converted (p < 0.0001). Sputum clearance produced by Immunoxel was equally effective across all forms of TB. In the immunotherapy arm the average weight gain was 2 kg, but placebo recipients gained only 0.6 kg. Immunoxel reduced TB-associated inflammation as evidenced by defervescence and normalization of elevated leukocyte counts and erythrocyte sedimentation rate. No adverse effects were seen at any time. The liver function tests indicate that ATT-caused hepatotoxicity was counteracted by Immunoxel. These results are in agreement with prior 20 trials of Immunoxel conducted over the past 17 years. CONCLUSION: Immunoxel is affordable, safe, effective, fast-acting, commercially available immunotherapeutic intervention to supplement conventional TB chemotherapy. Clinicaltrials.gov ID: NCT01061593.
Asunto(s)
Antituberculosos/uso terapéutico , Mezclas Complejas/uso terapéutico , Infecciones por VIH/terapia , Miel , Inmunoterapia/métodos , Tuberculosis Resistente a Múltiples Medicamentos/terapia , Tuberculosis Pulmonar/terapia , Administración Sublingual , Adulto , Método Doble Ciego , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Humanos , Masculino , Efecto Placebo , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/complicaciones , Tuberculosis Resistente a Múltiples Medicamentos/inmunología , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/inmunologíaRESUMEN
AIM: A 1-month Phase II trial was conducted in 41 patients with pulmonary TB who were randomized into treatment (n = 20) and placebo (n = 21) arms to investigate the safety and efficacy of an orally-administered therapeutic TB vaccine (V7) containing 10 µg heat-killed Mycobacterium vaccae provided by Immodulon Therapeutics Ltd (London, UK). MATERIALS & METHODS: Both arms received conventional anti-TB therapy administered along with a daily pill of V7 or placebo. The subject population had four categories of TB: drug-sensitive TB; retreated TB; drug-resistant TB; and TB with HIV distributed in V7 and placebo arms at 9:4:7:6 and 14:1:6:8 ratios, respectively. RESULTS: The mycobacterial clearance in sputum smears was observed in 72.2% (p < 0.0001) and 19% (p = 0.03) of patients on V7 and placebo, respectively. The average weight accrual among V7 recipients was 2.6 kg (p = 0.002) versus -0.2 kg (p = 0.69) in the control group. Except reduction in fever and increased lymphocyte counts, the changes in other secondary end points, such as hemoglobin, erythrocyte sedimentation rate and leukocyte counts, were not statistically different, although the proportion of patients responding favorably to V7 was invariably higher compared with placebo (p = 0.002). In control patients, no difference from baseline levels was noted except decreased hemoglobin content (p = 0.02). CONCLUSION: Oral M. vaccae was safe and has potential as an adjunct immunotherapy, targeting mucosal immunity, to improve efficacy and shorten treatment duration of TB chemotherapy.
Asunto(s)
Vacunas Bacterianas , VIH/inmunología , Mycobacterium/inmunología , Preparaciones Farmacéuticas/administración & dosificación , Tuberculosis Pulmonar/prevención & control , Administración Oral , Adulto , Carga Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana , Femenino , Infecciones por VIH/complicaciones , Calor , Humanos , Masculino , Persona de Mediana Edad , Placebos/administración & dosificación , Resultado del Tratamiento , Tuberculosis Pulmonar/complicaciones , Vacunas de Productos InactivadosRESUMEN
One-month Phase II trial was conducted in 43 sputum smear-positive patients with pulmonary tuberculosis randomized into treatment (n = 22) and placebo (n = 21) arms to investigate the safety and efficacy of an orally-administered therapeutic TB vaccine (V7) containing 10 µg of heat-killed Mycobacterium vaccae provided by Longcom company. Immunotherapy and control groups comprised 8 newly diagnosed (1stDx TB; 18.6%), 6 re-treated (RTB; 14%), and 29 multidrug-resistant (MDR-TB; 67.4%) cases distributed at 5:4:13 and 3:2:16 ratios, respectively. Both arms received conventional TB drugs administered under directly observed therapy. The average weight gain in V7 arm was modest, but statistically significant (0.6 kg; p = 0.004), while placebo patients lost 0.1 kg (p = 0.77). Except defervescence and increased lymphocyte percentage, other secondary endpoints such as erythrocyte sedimentation rate (ESR), leukocyte counts and hemoglobin content were not significantly affected. In control patients only one secondary endpoint, ESR, has improved. After one month mycobacterial clearance in sputum smears was observed in 31.8% (p = 0.03) and 9.5% (p = 0.83) of patients on V7 and placebo. However, the difference between outcomes in two arms was below significance threshold (p = 0.07). Thus, larger population of patients with prolonged follow-up is required to support these preliminary findings.
Asunto(s)
Inmunoterapia/métodos , Mycobacterium/inmunología , Vacunas contra la Tuberculosis/administración & dosificación , Vacunas contra la Tuberculosis/inmunología , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/terapia , Administración Oral , Adulto , Antituberculosos/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placebos/administración & dosificación , Esputo/microbiología , Resultado del Tratamiento , Vacunas contra la Tuberculosis/efectos adversos , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/efectos adversos , Vacunas de Productos Inactivados/inmunologíaRESUMEN
Placebo-controlled, randomized, phase 2b trial was conducted in 34 adults comprising 18 first-diagnosed (52.9%), 6 relapsed (17.6%), and 10 MDR-TB (29.4%) cases to investigate the safety and efficacy of an oral immune adjunct (V5). The immunotherapy (N = 24) and placebo (N = 10) arms received once-daily tablet of V5 or placebo for one month in addition to conventional anti-TB therapy (ATT) administered under directly observed therapy (DOT).The enlarged liver, total bilirubin, erythrocyte sedimentation rate, lymphocyte and leukocyte counts improved significantly in V5 recipients (P = 0.002; 0.03; 8.3E-007; 2.8E-005; and 0.002) but remained statistically unchanged in the placebo group (P = 0.68; 0.96; 0.61; 0.91; and 0.43 respectively). The changes in hemoglobin and ALT levels in both treatment arms were not significant. The body weight increased in all V5-treated patients by an average 3.5 ± 1.8 kg (P = 2.3E-009), while 6 out of 10 patients on placebo gained mean 0.9 ± 0.9 kg (P = 0.01). Mycobacterial clearance in sputum smears was observed in 78.3% and 0% of patients on V5 and placebo (P = 0.009). The conversion rate in V5-receiving subjects with MDR-TB (87.5%) seemed to be higher than in first-diagnosed TB (61.5%) but the difference was not significant (P = 0.62). Scoring of sputum bacillary load (range 3-0) at baseline and post-treatment revealed score reduction in 23 out of 24 (95.8%) V5 recipients (from mean/median 2.2/3 to 0.3/0; P = 6E-010) but only in 1 out of 10 (10%) patients on placebo (1.9/1.5 vs. 1.8/1; P = 0.34). No adverse effects or TB reactivation were seen at any time during follow-up. V5 is safe as an immune adjunct to chemotherapeutic management of TB and can shorten substantially the duration of treatment.