The Efficacy and Safety of Myelophil, [..] , for [CFS]: A Randomized Clinical Trial, 2019, Joung et al

[Andy]

Full title: The Efficacy and Safety of Myelophil, an Ethanol Extract Mixture of Astragali Radix and Salviae Radix, for Chronic Fatigue Syndrome: A Randomized Clinical Trial

Background: There is a strong demand for therapeutics to treat chronic fatigue syndrome (CFS), although there are limitations. Myelophil, which is a combination of extracts from Astragali Radix and Salviae Miltiorrhizae Radix, has been clinically used to treat fatigue-related disorders in South Korea. We conducted a randomized controlled clinical trial of Myelophil in patients with CFS and evaluated its efficacy and safety in two hospitals.

Methods: We enrolled 98 participants (M: 38, F: 60) with CFS in a phase 2 trial of oral Myelophil (2 g daily) or placebo for 12 weeks. The primary end point was a change in the Chalder fatigue scale, as scored by a numeric rating scale (NRS). The secondary end points included changes in the visual analogue scale, fatigue severity scale (FSS), and 36-item short-form health survey (SF-36). Biomarkers of oxidative stress and cytokines were evaluated by blood tests.

Results: Ninety-seven participants (48 in the Myelophil group and 49 in the placebo group) completed the trial. An analysis of all participants showed that Myelophil slightly improved fatigue symptoms compared with those of the placebo, but this effect was not statistically significant (p > 0.05 for the NRS, VAS, FSS, and SF-36). By contrast, an analysis of the subpopulation (53 participants, M: 24, F: 29) with severe symptoms (≥63, median NRS value of total participants) showed a statistically significant improvement in fatigue symptoms in the Myelophil group compared with the placebo (p < 0.05 for NRS, FSS, and SF-36). There were no significant changes in the biomarkers for oxidative stress and cytokines before or after the treatment. No Myelophil-related adverse response was observed during the trial.

Conclusion: These results support the hypothesis that Myelophil can be a therapeutic candidate to manage CFS and provide the rationale for its progression to a phase 3 clinical trial.

Open access, https://www.frontiersin.org/articles/10.3389/fphar.2019.00991/full

I'm dubious about the value of this paper but nice to see this bit

Only cognitive behavioral and exercise therapies have been recommended, although they only have partial benefits (Price et al., 2008; Larun et al., 2016). However, previous recommendations of these therapies that were based on a large-scale clinical study (called the “Pacing, graded activity, and cognitive behaviour therapy; a randomised evaluation” trial) were abandoned or revised in both the USA and UK due to serious criticism by both scientists and patients (Geraghty, 2017; Vink, 2017).

 

[Hutan]

It's nice to see research from South Korea. It would be great to hear more about what is happening there e.g. if there are patient organisations.

In the previous epidemiological studies that were conducted in Korea, the prevalence of CFS, as determined by the CDC criteria, was 0.6–1.2% (Kim et al., 2000, Kim et al., 2005).

I liked quite a lot about this paper. The write-up is clear; we know what they did, including what they did as post-hoc analyses. There's double-blinding and a control treatment. The partial funding from a manufacturer of the herbal medicine is declared. They managed to keep almost all of their participants throughout the trial. They were up front about the null result. They made a reasonable effort at checking for side effects. They say they are happy to share their data.

Clearly they are going to proceed on to a Stage 3 trial regardless, no doubt because the manufacturer of the herbal medicine is keen for that. But I think it's good that some of these herbs that so many of us try are tested in a rigorous way. If they get a positive result, will I believe it? Maybe not, because of the potential conflict, but hopefully a successful Stage 3 trial would mean that some completely independent work would be done. (Actually I have a soft spot for Chinese tonics with Astralagus and mushrooms and stuff - they taste so bad it's easy to imagine they are medicine.)

One bad point, which they acknowledge, is a vagueness around diagnosis. Participants had to answer diagnostic questions; there was no clinical diagnosis. I'm not sure about the diagnostic criteria; I'd have to look again, but they did have a requirement for 'PEM lasting more than 24 hours'. They may have a point that quite a few of their participants had very mild fatigue and that it is better to concentrate on more severely affected participants in future trials.

They used a modified Chalder Fatigue Scale. They are planning to use a different measure in future studies - if I've come across it before, I don't remember it.

At present, the Multidimensional Fatigue Inventory (MFI) is well applied in many clinical studies worldwide (Arnold et al., 2015; Maness et al., 2019). The MFI has five categories to evaluate multidimensional aspects such as reduced activity, cognitive impairment, and declining motivation, and the Korean version of MFI has been verified for its reliability and validity (Song et al., 2018). Accordingly, we need to consider the MFI as the primary end point and participants with moderate and severe symptoms of CFS in the next phase 3 trial with Myelophil.

It would be great to bring these researchers into the international community, to standardise approaches and so on.

 

[Trish]

I have done a quick search for the two herbs used. Both are commonly used in traditional Chinese medicine. Both have insufficiently researched claims of efficacy, and some warnings of side effects.

Here's a review of Astragalus mongholicus It is claimed to have all sorts of effects including as an immunostimulant and anti-inflammatory. It should be avoided by people with autoimmune conditions and those on immunosuppresant treatments.

Here's a systematic review of Salvia miltiorrhiza. It's used for treating cardiovascular disorders.

Both have lots of bioactive components that may interact with whatever other herbs they are mixed with.

Edited to change link.

 

[Snow Leopard]

The manuscript is decent but if you can't achieve significance with 49/48 patients, well, I doubt the therapy is very good.