Clinical Research
Copyright ©2008 The WJG Press and Baishideng.
World J Gastroenterol. Aug 14, 2008; 14(30): 4753-4762
Published online Aug 14, 2008. doi: 10.3748/wjg.14.4753
Table 1 Protocol for selection of patients for recruitment
Protocol for selection of patients for recruitment
Criteria for selection
Evidence of active pulmonary or extra-pulmonary tuberculosis
Age between 15 and 85 years
Readiness to comply with randomization, treatment and follow-up protocols
Patients giving written informed consent
Absence of diseases warranting treatment with systemic steroids, antimetabolites or warfarin
Concomitant conditions allowed
Patients with relapse, multiple relapse, treatment failure of DOTS regimen
Patients with hypertension, diabetes mellitus, COPD (chronic obstructive pulmonary disease) with continuation of required medications
Patients with asthma on inhalational steroid
Skin conditions requiring topical small area steroid application
Patients with HIV positivity but without symptoms suggestive of AIDS
Hepatitis B/C virus carrier
Criteria for rejection
Presumptive diagnosis or lack of evidence of active tuberculosis
Age < 15 or > 85
Patients taking other alternative therapies for tuberculosis
Patients declining to give consent or comply with protocol
Pregnant females
Heavy alcoholism history, > 80 g of alcohol/d for males and > 20 g of alcohol/d for females[50]
Concomitant conditions not allowed
Preexisting liver disease with AST, ALT raised > twice upper normal, evidence of portal hypertension.
Preexisting renal disease with S. Creatinine raised > twice upper normal
Sickle cell disease with history of crisis, anemia and jaundice
History of gout
Recent drop-outs from other TB centers due to complications and side effects
Patients on steroid and/or antimetabolite for other collagen, auto-immune or neoplastic diseases
Table 2 Chemical constituents of formulation
Chemical constituents of formulation with active principles
Chemical constituents of curcuma longa with active principles
CurcuminoidsDesmethoxycurcumin
Bisdesmethoxycurcumin
Curcumin
TurmeronesAr-turmerone
α-turmerone
β-turmerone
Curcumenesγ-Curcumene, ar-Curcumene, Dehydrocurcumene
zingiberene
β-bisabolene
β-sesquiphellandrene
MiscellaneousTerpinolene, P-Cymene, 1-8-Cineole, Curlone
Chemical constituents of Tinospora cordifolia with active principles
AlkaloidsBerberine, Palmatine,Tembetarine,
Magnoflorine, Choline,Tinosporin,
Isocolumbin, Tetrahydropalmatine
Glycosides18-norclerodane glycoside,
Furanoid diterpene glucoside,
Tinocordiside,Tinocordifolioside,
Syringin, Syringin-apiosylglycoside,
Palmatosides C, PalmatosidesP
Cordifolioside A, Cordifolioside B
Cordifoliside- A, -B, -C, -D and -E
Diterpenoid LactonesFuranolactone, Clerodane derivatives,
Tinosporon, Tinosporides, Jateorine,
Columbin
Steroidsβ-sitosterol, δ-sitosterol, 20β-hydroxyecdysone
Ecdysterone, Makisterone A, Giloinsterol.
SesquiterpenoidTinocordifolin
Aliphatic compoundsOctacosanol, Heptacosanol, Nonacosan-15-one
Miscellaneous compounds3, (α, 4-dihydroxy-3-methoxy-benzyl)-4-(4- hydroxy-3-methoxy-benzyl)- tetrahydrofuran,
Jatrorrhizine, Tinosporidine, cordifol, cordifelone
N-trans-feruloyl tyramine as diacetate, Giloin, Giloinin
Tinosporic acid
Table 3 Baseline demographic and disease characteristics in the intention-to-treat population
Characteristics of patientsControlTrialP
Sex
Male (%)104 (54)169 (53)0.934
Female (%)88 (46)147 (47)0.927
Age-yr median(IQR 25th & 5th)35 (23.75-45)35 (27-45)0.229
Weight (kg, mean ± SD)37.61 ± 5.9438.32 ± 6.080.199
Ethnicity (%)1
Tribals171(89)287(91)0.883
Others21(11)29(9)0.559
Habits (%)
Smoking58 (30.2)103 (32.6)0.685
Alcohol23 (12)33 (10.4)0.633
Both26 (13.5)53 (16.7)0.403
Socio-Economic status (%)
Upper-Middle20 (10.4)40 (12.6)0.499
Middle30 (15.6)52 (16.4)0.833
Lower142 (74)224 (71)0.763
Pulmonary (%)2
Open cases (sputum +ve)67 (35)137 (43.4)0.214
Parenchymal152 (79.2)258 (81.6)0.822
Cavitary18 (9.4)66 (21)0.003
Effusion9 (4.6)20 (6.3)0.464
Fibrosis27 (14)68 (21.5)0.081
Extra pulmonary (%)2
Cervical lymph node18 (9.4)31 (9.8)0.883
Abdominal4 (2.1)6 (2)0.886
Laryngeal7 (3.6)11 (3.5)0.925
Central nervous system6 (3.1)6 (2)0.389
Bones/Joints10 (5.2)19 (6)0.72
Skin03 (1)0.598
Genito-Urinary2 (1.04)1 (0.3)0.304
Type of case (%)
New140 (73)195 (61.7)0.245
Relapse43 (22.4)97 (30.7)0.122
Chronic9 (4.7)24 (7.6)0.225
Hematology
Hb (%)8.84 ± 1.938.95 ± 1.950.808
Total leucocyte count/mm310 179 ± 4 6809575 ± 40750.478
ESR66.79 ± 30.6470.49 ± 27.910.517
Liver Function (mean, 95%CI)
Serum bilirubin1.07 (0.7-1.3)1.09 (0.8-1.4)0.952
AST34.35 (17-63) 32.4 (11-61)0.658
ALT27.45 (9-57)31.15 (6-52)0.655
ALP100 (50-260)107 (50-260)0.092
Table 4 Effects of herbal formulation on incidence, onset, duration and severity of hepatitis
ATT induced hepatitis outcome (Table 2)Control (n = 192)Trial (n = 316)P
Patients with raised AST (%)27 (14)2 (0.63)< 0.0001
Patients with raised S bilirubin (%)17/27 (63)0< 0.0001
Mean onset of hepatitis symptomatic49.12 ± 17.22-< 0.0001
Mean onset of hepatitis asymptomatic29.9 ± 17.6339 ± 11.310.443
Mean onset of any hepatitis42 ± 19.4839 ± 11.310.776
Mean duration of raised AST27.5 ± 7.2521< 0.0001
Hepatitis gradation
Grade-I102< 0.0001
Grade-II90< 0.0001
Grade-III80< 0.0001
Grade-IV00
Reinstitution of ATT in patients (%)22/27 (81.5)NA
Table 5 Comparison of liver enzymes and bilirubin in patients developing hepatitis
Control (n = 27)Trial (n = 2)P
AST195.93 ± 108.7485 ± 4.24< 0.0001
ALT75.74 ± 26.5441 ± 1.41< 0.0001
AST/ALT2.35 ± 0.742.08 ± 0.180.207
ALP241.74 ± 140.96147.5 ± 45.960.118
Serum bilirubin5.4 ± 3.41.5 ± 0.42< 0.0001
Table 6 Effects of herbal formulation addition on disease outcome
Treatment outcome for ATTControlTrialP
Number of sputum +ve case at start (%)67/192 (35)137/316 (43)0.03
Number of sputum +ve case after 1-month of treatment (%)10/67 (14.93)4/137 (2.9)0.0068
Poorly resolved parenchymal lesion (%)9/152 (5.92)2/258 (0.78)0.0037
Failure to improve functional status (%)19/192 (10)6/316 (2)0.00013
Treatment dropouts (%)10/192 (5.2)00.0001
Weight (kg)39.17 ± 5.540.65 ± 6.220.0016
Hb (%)10.92 ± 2.0111.17 ± 1.970.176
ESR mm in 1st hour45.96 ± 18.5238.84 ± 22.370.0001