RCT (Phase II) conducted by Makerere University's School of Health Sciences, Uganda.
Latest update (February 2016)
Much of the data has been analysed and exciting findings are emerging...
... and what's becoming ever more evident is that moxa may be a viable adjunctive treatment for MDR-TB.
Here is a summary of the findings so far:
Moxa significantly improves sero-conversion to 'sputum-negative' status in the first month of TB treatment. But there was also a significant positive difference in the last four months of treatment in those few patients who had still not sero-converted by that time (i.e. significantly fewer in the moxa group than in the non-moxa group). Both are very exciting findings given what they imply for drug-resistant cases (when treatment takes four times longer and the success rates are nearly half what they are for ‘normal’ TB). With the benefit of this data we can now seriously suggest that similar findings could be game-changing for treating drug-resistant cases.
In HIV co-infected cases this response was slower but was still significant.
Moxa appears to significantly improve adherence to TB drug therapy. (We have to add that we suspect that this may be a psychological effect of some kind, or possibly an effect of greater attention from the clinical staff at the health centre. The study doctor was blinded to the randomisations, but the study nurses couldn’t be and we know that they were as keen as we were to see good results. Maybe they just couldn't help but try to help to see this happen by being especially attentive!).
Moxa promotes a significant improvement in CD4 count in both HIV-positive and in negative TB cases compared with those in the non-moxa group. (CD4 are the immune cells that crash with HIV/AIDS and are the primary markers to indicate advancement of disease). We must add that have to share our astonishment that this finding has never been elucidated before because of what it may imply.
With the HIV patients split out from the whole cohort and then statistically analysed these differences in CD4 count in the HIV-positive moxa patients were found to be more significant than it was in the whole cohort. The effects of the moxa do seem to come through a little more slowly, however (which may not be so surprising since with HIV the immune response is already more dulled). We should add here that we remain a little cautious about this finding because the data doesn't show when patients started their HIV anti-retroviral therapy (whether it was shortly before TB treatment beginning or a long time before). It's possible this could make a difference (in fact it might even show this finding to be more significant) but the team reckons that this information is recoverable from the piles of existing files so this uncertainty should be clarified in the course of the next few weeks.
There was significantly more fever at 4 months occurring amongst non-moxa patients than the moxa group (we’re not sure why this occurred or whether it means anything).
The moxa group recorded significantly less weight gain compared with the non-moxa group. (This surprised us, though again we’re not sure yet what this means. It was certainly not something we expected given what we were told by both patients and health workers in the pilot studies.)
Moxa promotes a statistically significant rise in hemoglobin levels. This wasn’t something we were particularly looking for. We’re still not sure what sort of significance this may have but are pretty confident that it’s positive. We intend to find out more from the existing literature in Japan, and also by learning more about the patterns of haemoglobin changes that normally occur during TB treatment.
With the HIV patients split out and analysed as a sub-group the differences in haemoglobin levels are more significant in the moxa patients than in the non-moxa.
One early finding appears to have disappeared in this analysis, at least temporarily. This finding related to a reduction of one of the key side-effects from the TB drugs (joint pain). According to an earlier preliminary analysis of the first ninety patients by the study doctor this side-effect was experienced significantly less in the moxa patients. When a broad analysis was made of all the 180 patients after completion, however, there were no apparent differences in the data. This related specifically to ‘musculo skeletal' as a data category, however, and not specifically to 'joint pain'. This discrepancy is going to be reviewed in the hope of picking out the joint pain notifications retrospectively. If it’s still there we would like to identify it!
We have no x-ray analyses yet. The study doctor is sure that they will show some interesting findings given the other data which would further indicate an improved recovery response. He believes that this will make the findings more scientifically robust (more so even than the blood data which we know can easily temporarily alter depending on the time of the day or on stress levels).
The karnofsky ‘well-being’ scores (which the professor put a lot of store by) have turned out to have been a let-down – the recorded differences ended up being inconsequential, possibly because it's not sensitive enough a measure to be suitable for ambulatory TB outpatients, and is actually more suitable for measuring recoveries in hospitalised patients with more advanced disease.
These findings relate to orthodox DOTS chemotherapy (‘directly observed treatment short-course’) – for treatment of drug-susceptible tuberculosis (DS-TB). In Uganda this comprises an intensive treatment of two months using four drugs followed by a continuation phase of six months with two. If these results are considered in the light of the much longer treatment of drug-resistant tuberculosis (DR-TB) which uses more drugs which are both weaker and more toxic they throw up some exciting possibilities.
DR-TB is sub-classified clinically as being either Multi-Drug Resistant (MDR-) or Extensively Drug-Resistant (XDR-) depending on the extent of the resistances to the various anti-TB drugs. In the current study all enrollable or enrolled cases who were confirmed as DR were automatically removed or excluded from the cohort in accordance with the stipulations within the original study design.
So these numbers tell us nothing specific about DR cases, but they do suggest something potentially very interesting if they are conjecturally extrapolated for the much lengthier treatments for DR disease particularly because these types of TB are recognised to be much more dangerous.
Both MDR- and XDR-TB cases experience a much longer intensive phase of treatment with more drugs used. Treatment comprises a minimum six month intensive phase with six drugs used (including daily injections), and then (subject to successful bacteriological conversion) a subsequent eighteen month continuation phase using four drugs. This extended treatment is well recognised as having a much lower success rate than DOTS (50% successful completion for MDR cases and a terrible20% for XDR ones, as opposed to 87% for DOTS for DS-TB). Incompletion of treatment is commonplace and is considered to be often caused by the pernicious side-effects of the drugs. Less successful cure rates are also considered to be because of their lesser efficacy.
What these findings suggest is that there is a moxa-induced host response which is statistically significant in the early stages of the multi-drug DOTS therapy in a proportion of the moxa patients. (It should be noted that this effect could possibly be enhanced if the moxa dosage was increased. The dosage used in the study was deliberately minimised in order to maximise treatment adherence in moxa patients and therefore render the study statistically viable.)
We now believe that it is entirely possible that a similar response to that recorded above might be seen in patients undergoing treatment for DR-TB with adjunctive moxa regardless of the extent of the drug-resistance of the tuberculosis strain. If this were to occur in DR patients on much longer treatment regimens with weaker drugs which are hundreds of times more expensive and far more toxic then these statistical differences could be even more significant than in this current cohort of DS-TB cases and moxa might even contribute to improved treatment outcomes. Furthermore such a response could well be found to be enhanced not just during the intensive phase but also over the whole treatment period, as a result of which treatment regimens might even be safely reduced in some cases.
Principle Investigator of the study:
Professor Paul Waako (MBChB) MSc. PhD, Associate Professor and Head of Department Pharmacology and Therapeutics, College of Health Sciences, Makerere University Medical School , Kampala, Uganda.
"A 12 month pilot study with TB patients in Kampala suggested that daily use of moxa can improve the recovery rate and reduce the side effects of medication. This is now being expanded into a Randomised Control Trial to investigate in more detail the effects of moxa on immune responses, recovery rates and quality of life. The study will involve 180 patients presenting as new cases of TB, either with or without HIV co-infection. All patients will receive the standard TB medication according to their condition. In each group (+/- HIV), half of the patients will be trained in self-administration of daily moxa treatment for 8 months. Regular monitoring of all patients will be carried out , with analysis of sputum and blood, radiological monitoring, clinical examinations and assessment using the Karnovsky score. Patients will be withdrawn from the study in the case of non-compliance or any adverse symptoms or disease complications."
The study was carried out at Kiswa Health Centre, Kampala, Uganda.