Randomized Clinical Trial: IS Zinc and Zinc Ionophere EGCG as Supplement Improve Outcome of Active Pulmonary Tuberculosis
Primary Purpose
Tuberculosis
Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
zinc 50 mg + Epigallocatechin gallate
Sponsored by
About this trial
This is an interventional treatment trial for Tuberculosis
Eligibility Criteria
Inclusion Criteria:
- new diagnosed pulmonary positive t.b patients
- age above 18 years
- any patients with HIV and immuncromoised with t.b patients
- patients with covid 19 and t.b
- patients with drug t.b resistant
- male or female
- all races African or Asian or white -
Exclusion Criteria:
1- less than 18 years 2- pregnant female 3- on another supplement
-
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
100 pulmonary positive patients on tb protocol adding to supplement zinc 50 mg 400 mg once daily
control group 100 patients only on tuberculosis national protocol
Arm Description
Outcomes
Primary Outcome Measures
sputum analysis at start of treatment and after one month
percentage of conversion sputum samples converted from positive to negative after one month
Secondary Outcome Measures
measurement of serum or plasma zinc at all participants
measurement of serum interleukin 6
measurement of serum interleukin 6
serum Adenosine deaminase (ADA)
measurement of serum Adenosine deaminase (ADA)
Full Information
NCT ID
NCT05116098
First Posted
October 20, 2021
Last Updated
November 1, 2021
Sponsor
Ministry of Health, Saudi Arabia
1. Study Identification
Unique Protocol Identification Number
NCT05116098
Brief Title
Randomized Clinical Trial: IS Zinc and Zinc Ionophere EGCG as Supplement Improve Outcome of Active Pulmonary Tuberculosis
Official Title
Randomized Clinical Trial: IS Zinc and Zinc Ionophere EGCG as Supplement Improve Outcome of Active Pulmonary Tuberculosis
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 30, 2021 (Anticipated)
Primary Completion Date
June 30, 2022 (Anticipated)
Study Completion Date
November 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ministry of Health, Saudi Arabia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Tuberculosis is still global burden disease at all the word and effect on quality life of patients and affect on health authorities because the cost of medicine and health cost .
A total of 1.4 million people died from TB in 2019 (including 208 000 people with HIV). Worldwide, TB is one of the top 10 causes of death and the leading cause from a single infectious agent (above HIV/AIDS).
In 2019, an estimated 10 million people fell ill with tuberculosis (TB) worldwide. 5.6 million men, 3.2 million women and 1.2 million children. TB is present in all countries and age groups. But TB is curable and preventable.
In 2019, 1.2 million children fell ill with TB globally. Child and adolescent TB is often overlooked by health providers and can be difficult to diagnose and treat.
In 2019, the 30 high TB burden countries accounted for 87% of new TB cases. Eight countries account for two thirds of the total, with India leading the count, followed by Indonesia, China, the Philippines, Pakistan, Nigeria, Bangladesh and South Africa. ( WHO) All TB cases and 92.5% controls were zinc deficient. The odds of TB cases with deficiencies of vitamin A and zinc was 2.3 (95% CI: 1.1 to 4.8) times more likely as compared to the controls. More than 80% of all participants had below average fulfilment of energy and vitamin A intakes. (7) Zinc is necessary for intact immune health and defense against infection but there are common health problem deficiency at developing countries and so zinc needs as supplement and the second problem zinc need helper for transfer through plasma membrane so zinc ionophore is a best solution as this problem so the investigators can use zinc ionophore as helper for zinc to enter the cells for autophagy
Detailed Description
M. tuberculosis -infected PMs, in vitro, elaborated IL-6 as the only major cytokine, which was significantly inhibited by anti-TB drugs. Therefore, IL-6 can be developed as a potential biomarker or biosignature to assess the success of the treatment of TB. (1) Tuberculosis is a global health problem, and there is even an increase in cases of multidrug-resistant tuberculosis in the world. Therefore, research is needed that can find new anti-tuberculosis drugs (OAT) that are more effective for tuberculosis treatment. In this study, the effect of (-)-epigallocatechin-gallate (EGCG) of tea leaves (Camellia sinensis) combined with the first-line OAT will be observed, in order to find out whether EGCG has anti-tuberculosis activity and can increase the potential of first-line OAT in-vitro. The anti-tuberculosis activity of EGCG was determined by broth dilution method using Middlebrook 7H9 media at concentration of 50, 100, 150, dan 200 ppm, then the potential of first-line OAT before and after combined with the EGCG was observed. The results showed that the activity of EGCG at concentration 50 ppm and 100 ppm could inhibit the Mycobacterium tuberculosis growth by 80%, at concentration 150 ppm by 90%, and at concentration 200 ppm by 100%. First-line OAT activity before combined with EGCG was ≥ 90% at 5 ppm rifampicin, 0.5 ppm isoniazid, 50 ppm pyrazinamide, and 5 ppm ethambutol. Whereas after combined with EGCG, the potential of each drug increased, marked by anti-tuberculosis activity achieved ≥ 90% at lower concentrations, i.e. rifampicin 0.5 ppm, isoniazid 0.25 ppm, pyrazinamide 20 ppm, and ethambutol 2 ppm. These results indicated that the potential of each first-line OAT increases after being combined with EGCG, and EGCG has potentiation effect when combined with those drugs. In conclusion, EGCG can increase the first-line OAT activity (2)
The down-regulation of TACO gene expression by epigallocatechin-3-gallate was accompanied by inhibition of mycobacterium survival within macrophages as assessed through flow cytometry and colony counts. Based on these results, the investigators propose that epigallocatechin-3-gallate may be of importance in the prevention of tuberculosis infection. (3) The effectiveness of anti-tuberculosis treatment was improved during the first two months by vitamin A and zinc supplementation," Dr. Clive E. West, a professor in the department of nutrition at Wageningen University in the Netherlands, and colleagues write in the April issue of the American Journal of Clinical Nutrition (2002;75:720-727). Previous research has shown that TB patients often suffer from malnutrition, which can weaken immune response and increase disease susceptibility. The addition of vitamin A and zinc has been observed to boost the immune response in these patients. Patients who received the supplements were twice as likely to have eliminated the TB bacteria from the mucus coughed up from their lungs by two weeks than the group receiving only standard drug treatment, and maintained that difference for seven weeks. These patients also had a greater reduction in abnormalities or lesions on their chest x-rays than those not taking the supplements. Reducing the amount of potentially contagious bacteria present in patients' sputum would cut the rate at which they spread TB to others, the researchers noted. (4) The effect of green tea extract supplementation on sputum smear conversion and weight changes in pulmonary TB patients: A randomized controlled trial (5) Zinc is an essential micronutrient (34, 40-42), and its tissue and plasma levels are influenced by dietary intake (38, 42). While severe zinc deficiency is rare in the developed world, moderate zinc deficiency is widespread, concentrated in elderly populations (42-45), and can be exacerbated in critically ill patients (33, 46-49). the investigators demonstrate that both genetic MT deficiency and dietary zinc deficiency potentiate lung injury in mechanically ventilated mice, consistent with an essential role for the zinc/MT system in protecting the lung from injurious stretch. To demonstrate clinical relevance of our findings, the investigators show that humans who go on to develop ARDS exhibit lower plasma zinc levels. Taken together, our results suggest that failure of essential stretch-adaptive responses, in this case associated with a remediable dietary deficiency among hospitalized patients, may play an important role in injury responses propagated by MV. (6)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
100 pulmonary positive patients on tb protocol adding to supplement zinc 50 mg 400 mg once daily
Arm Type
Active Comparator
Arm Title
control group 100 patients only on tuberculosis national protocol
Arm Type
Placebo Comparator
Intervention Type
Combination Product
Intervention Name(s)
zinc 50 mg + Epigallocatechin gallate
Intervention Description
ZINC 50 MG and EGCG 200mg oral daily for 1 month
Primary Outcome Measure Information:
Title
sputum analysis at start of treatment and after one month
Description
percentage of conversion sputum samples converted from positive to negative after one month
Time Frame
6 month
Secondary Outcome Measure Information:
Title
measurement of serum or plasma zinc at all participants
Time Frame
6 month
Title
measurement of serum interleukin 6
Description
measurement of serum interleukin 6
Time Frame
6 month
Title
serum Adenosine deaminase (ADA)
Description
measurement of serum Adenosine deaminase (ADA)
Time Frame
6 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
new diagnosed pulmonary positive t.b patients
age above 18 years
any patients with HIV and immuncromoised with t.b patients
patients with covid 19 and t.b
patients with drug t.b resistant
male or female
all races African or Asian or white -
Exclusion Criteria:
1- less than 18 years 2- pregnant female 3- on another supplement
-
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Randomized Clinical Trial: IS Zinc and Zinc Ionophere EGCG as Supplement Improve Outcome of Active Pulmonary Tuberculosis
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