Upcoming USA study for LDN and arthritis pain/functioning, RA/SA disease activity

[ITYFIALMCTT]

There's been mention of LDN (low dose naltrexone) in the comments of recent threads.

I was interested to see that there's a clinical trial protocol (not yet recruiting) in the USA to assess LDN (low dose naltrexone) for the relief of arthritis pain (osteoarthritis; rheumatoid, and psoriatic) and alteration in disease activity (RA only) or BASDAI (SA only).

It's a small trial but they've made it randomised and crossover so that's a decent trial design. I'll be interested to see what happens during the recruitment phase and any outcome. I'll say upfront that I don't know enough about LDN to understand whether 4.5mg is an acceptable dosage and if it's feasible to expect people to experience relief or change in their disease activity during the 8 weeks they're scheduled to be on it (they'll be on placebo for the other 8 weeks).

clinicaltrials.gov/ct2/show...

ETA: for people who haven't seen it, ScienceBased Medicine has a piece by neurologist Steve Novella from 2010 about LDN that is clear-eyed about the (then) state of the research: sciencebasedmedicine.org/lo...

I don't know anything about LDN research tho' a search on a clinical databases showed some recently published research (still pilot and small scale as noted by Novella).

[Simba1992]

Interesting. Finally research on LDN and RA!

[Simba1992]

It seems to be very individual how people react to LDN. Some have quite immidiate response while for some it may take up to 4m. Doctors who have been using it for a longer time on their patients have the experience that in RA the reaction comes often later. They have also seen that 10-15% do not respond to LDN.

The max dose is 4,5mg but it is not always the optimal dose, some feel better with very small doses this is why you start with 0,5mg and slowly work yourself up to your sweet spot.

[Lucy11]

Interesting. The main reason for the study is for pain relief.

If I understood correctly the people who posted on this site that were using LDN were doing so in lieu of DMARDS whether biological or otherwise?

In this study participants will be able to stay on whatever medication they are taking just not be allowed to add any that is explicitly used for pain.

For those of you using LDN are you using it for the sole purpose of pain relief or also because you believe it has disease modifying benefits?

[ITYFIALMCTT in reply to Lucy11]

As you say above, pain and function is the primary outcome and there are several secondary outcomes (e.g., the particular disease activity scores and CRP changes).

One of the exclusion criteria is:

Current use of opioids including tramadol

The exclusion makes sense as naltrexone is an opioid antagonist so it might reduce the impact of such medication albeit I though it had to be in dosages substantially larger than LDN.

After a quick look at Entrez Pubmed and Cochrane, there are more trials than I thought that look at LDN and inflammation but a mixed bag as to the condition and the quality of the trial design. ncbi.nlm.nih.gov/pubmed/?te...

[Lucy11 in reply to ITYFIALMCTT]

Aha. I see, but if they're allowed to stay on say, MTX, or Humira , etc. that would be a limitation in the study, no? (Not for pain, but for disease activity).

What's to say that it's not one of the DMARDS working on slowing the disease, lowering CRP, or DAS?

[ITYFIALMCTT in reply to Lucy11]

I'm torn on this. Strictly speaking the answer is that this is probably why the researchers have opted for a randomized, double-blinded, cross-over, placebo-controlled trial design.

I'm not au fait with either LDN nor inflammatory arthritis research so can't begin to understand whether it's feasible for there to be a shift in an 8 week period on either the intervention or the placebo that would allow a comparative assessment with the other arm and for the condition versus the baseline.

Baseline evaluation and ready access to the health records (which they seems to have as this is a VA trial) might well reveal whether the DMARDs are kicking in or, contrariwise, beginning to fail someone? It's equally possible to posit that a participant might have been stable with DMARDs but they've lessened their impact or started to fail during the trial.

tbh, I'm a little surprised that they have calculated that 60 participants is sufficient to yield a power with a decent effect size: "small but placebo-controlled study, powered to detect an effect size as small as that seen with NSAIDs or the most beneficial non-pharmacologic approaches".

That said, I'm thinking about this as 3 groups of 20 (each as their own control) and maybe the NSAID research *is* based on similar effect sizes that are yielded by 60 overall participants.

[Simba1992]

There has been a lot of commotion around the effects of LDN on Chrons, MS and Fibromyalgia as well as pain reduction. The research has also been concentrated on above AI diseases. I have been wondering about the lack of studies on RA. My immidiate thought was that the diseases listed above have no clear gold standard treatment protocol with Pharma meds while RA does, and is strictly followed by FDA and NHS, with a lot of money involved for Pharma and questioning this protocol would be too controversial. Just me thinking🤔. On the other hand it may be that the effect on RA has less anecdotal evidence of efficacy and thus less interest for reaserch (?).

[nomoreheels in reply to Simba1992]

I've been looking/bit of research lately & I think it's the latter. I think there are too many other suitable disease-specific meds for RD. I don't think money is the issue, whilst the NHS is cash strapped NICE wouldn't recommend it for MS if it didn't work for that, not so for RD & associated conditions.

[ITYFIALMCTT in reply to Simba1992]

Where there is a gold-standard treatment protocol it would breach the Helsinki Declaration for the conduct of clinical trials to have participants who are not following that protocol. (That's a simplification but mostly true as some major countries have not signed the Helsinki Declaration.)

It's one of the reasons trials end up demonstrating equivalence in efficacy etc. Or, as for this design, you can *add* something to the standard of care protocol but it wouldn't be ethically acceptable to remove a core element - e.g., the anti-inflmmatory drugs, DMARDs etc.

[Simba1992 in reply to ITYFIALMCTT]

Interesting, didn't know that!