A 29 week randomised, double-blind, placebo controlled, parallel design, single centred phase 2 study to assess the efficacy of individualised homoeopathic treatment as add on therapy in management of asthma in atopic or non-atopic subjects.

PROTOCOL SYNOPSIS 

Title of the project

A 29 week randomised, double-blind, placebo controlled, parallel design, single centred phase 2 study to assess the efficacy of individualised homoeopathic treatment as add on therapy in management of asthma in atopic or non-atopic subjects.

|Phase of the trial

Phase 2

|Indication

To be administered as an add on therapy to the standard of care asthma therapy (SOCAT) based on GINA report 2021 in asthmatic subjects who are atopic or non-atopic

|Study Objectives

Primary objective:

To determine if addition of individualised homoeopathic medicine to the standard of care asthma treatment in atopic and non-atopic subjects who have asthma is useful in asthma management measured by

1. Better asthma related quality of life,

2)Better lung function as compared with standard of care asthma treatment alone in 28 weeks.

Secondary Objective:

To determine if addition of individualised homoeopathic medicine to the standard of care asthma treatment in atopic and non-atopic subjects who have asthma is associated with improvement in atopic status measured by decreased

1)  Total serum IgE levels,

2. Decreased AEC,

3. Decreased sputum eosinophils count

| Study Design

This is a randomised, double blind, placebo-controlled, parallel, single centred phase 2 trial to evaluate the efficacy of individualised homoeopathic medicine as an add on therapy in asthmatic subjects with or without atopy.

Approximately 60 subjects will be enrolled, 30 on each arm. Eligible mild to moderate asthma patients with documented allergy will be enrolled. This trial consists of 4 stages 1) screening,2) Randomization,3) treatment,4) follow up. During screening phase each patient will provide informed consent prior to randomization.

 After collection of baseline data patients will be randomised on homoeopathic medicines arm or homoeopathic placebo arm in the ration of 1:1 for a period of 24 weeks.

The randomization of subjects to study groups will be based on a randomization scheme that will be reviewed and approved by an independent statistician.

Both the arms shall receive standard of care asthma therapy based on GINA report 2021 for a period of 24 weeks. The expected duration of trial participation is 29 weeks.

| Study end points

primary endpoint:

1. The change in mean overall AQLQ score from base line in 28 weeks

2. The change in FEV1 from base line in 28 weeks

 Secondary endpoints:

1. Percentage of atopic subjects showing improvement in the atopic status demonstrated by total serum IgE level from baseline till the end of 28 weeks.

2. Percentage of subjects who had raised AEC at the baseline and show decrease in AEC from baseline to end of 28 weeks

3. Percentage of subjects who had raised Sputum eosinophils count at baseline showing decrease in Sputum eosinophils count from baseline till end of 28 weeks.

 Safety endpoints:

1. ACT

2. Total Number of Adverse Events

3. PEF readings

4. Abnormal Physical Examination Finding

5. Abnormal Vital sign values

6. Abnormal ECG findings

7. Clinically Significant Abnormal laboratory findings

 

Study treatment

Test arm:

1. Standard of care asthma treatment as defined by GINA guidelines 2021

2. Orally administered centesimal/ LM potencies of Individualised homoeopathic medicines in globule and/or liquid OD dose for 24 weeks

Control arm:

1. Standard of care asthma treatment as defined by GINA guidelines 2021

2. Orally administered globules or liquid homoeopathic placebo in OD dose for 24 weeks

| Inclusion criteria

1. Properly completed patient informed consent

2. Male or female aged at least 18 years /Children above 12 years can be included

3. Clinical history consistent with asthma.

4. Diagnosed asthmatics who may or may not be receiving treatment shall be inclusive.

5.Willingness and ability to sign ethics committee approved Informed Consent Form shall be inclusive. In case of illiterate subjects signature of an LAR shall be acceptable.

|Exclusion criteria

1. Infants and children below age of 12 years shall not be eligible.

2. Pregnant and nursing women shall be excluded.

3. Subjects having a history or symptoms of viral infection with in past 1 week shall be excluded.

4. Subjects having an acute exacerbation of asthma within 4 weeks shall be excluded for spirometry.

5. Subjects requiring oral corticosteroids shall be excluded.

6. Subjects not withholding prohibited drugs for the specified time period shall be excluded.

7)Subjects suffering from life threatening diseases will be excluded.

8. Subjects having a history of near fatal asthma requiring intubation and mechanical ventilation will be excluded.

9. subjects with history of hospitalisation for asthma in past 1 year will be excluded.

10. Subjects having history of anaphylactic reaction in the past will be excluded.

11. Subjects taking any homoeopathic therapy or preparation in any form shall be excluded.

12. Asthmatic with food allergy as a trigger for asthma will be excluded.

13. Subjects with COPD shall be excluded.

|Sample size

Considering approximately 10% drop-out, in total 60 patients will be enrolled for the study in order to get 50 evaluable patients. A total of 60 patients will be randomized to one of 2 treatment groups in ratio of 1:1 (i.e., 30 patients per treatment group) so as to have 27 evaluable patients per treatment group i.e, completing the primary analysis (end of week 29) visit in the trial.

| Statistical Analysis

Unless otherwise stated, all hypotheses will be tested at a significance level of 0.05 and 95% confidence interval. Data will be analyzed using R software version 4.0 or higher with appropriate statistical tests. The descriptive statistics for continuous variables will be presented with the number of subjects (n), mean, standard deviation (SD), median, minimum, and maximum value. For categorical data, the descriptive statistics will be presented with frequency (count and percent) of subjects falling within the category. Descriptive analyses will also include graphical presentations of data, wherever appropriate. The p-values will be displayed. The Statistical analysis plan will contain a more comprehensive explanation than described above of the methodology used in the statistical analyses. The Statistical analysis plan will also contain the rules and data handling conventions used to perform the analyses, and the procedure used for accounting for missing data.

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