Open NIH: Proof of concept trial on the effect of Ketamine on Fatigue Study

[Sly Saint]

The National Institute of Nursing Research (NINR), at the National Institutes of Health
(NIH) is seeking people who are cancer survivors or have a chronic illness such as myalgic
encephalomyelitis (ME), chronic fatigue syndrome (CFS), Sjogren’s disease, or
Lupus to
participate in a research study on fatigue. Fatigue is a common side effect of various
illnesses. Researchers want to test if a one
-time dose of the medication Ketamine or a
similar drug can reduce fatigue. This is not a treatment study for fatigue, cancer, ME, CFS,
Sjogren’s disease, or Lupus. Study procedures and medications are provided at no cost.
Travel costs for study visits will be reimbursed in accordance with NIH guidelines.

full details
https://www.cc.nih.gov/sites/nihinternet/files/internet-files/recruit/pdfs/20_fatigue.pdf

(this pdf seems to have been created last year?)

 

[James Morris-Lent]

Obvious question - why Ketamine?

Also the wording: "research study on fatigue...not a treatment study for fatigue..." - huh??

 

[Invisible Woman]

Could be they want to learn something about how ketamine works or affects certain systems in the body? Or just compare the reaction of ketamine to the "active" placebo?

So, the research is addressing a treatment for something rather than any of the diseases listed?

Given that I am assuming they are assuming that fatigue experienced by all those groups is
a) the same symptom & I'm not sure it is
&
b) it has similar causes & I'm not at all convinced about that.

It might be interesting to see if medication targeted at "fatigue" experienced by different groups yields different effects but that certainly doesn't sound like that's happening here.

 

[rvallee]

Obvious question - why Ketamine?

Also the wording: "research study on fatigue...not a treatment study for fatigue..." - huh??

It's been found potentially useful for depression, although that hasn't actually panned out. You can make the rest of leap yourself, it's a very short hoppity-hop.

 

[Invisible Woman]

It's been found potentially useful for depression,

Yes, that too & in more ways than one. It's also been known to cause it. A neighbour's grand daughter experimented with it during her first year and uni. That was a few decades ago now.

She went from a bright young thing with everything ahead of her to suffering from very severe depression, unable to hold down a job or maintain a relationship.

 

[5vforest]

So they won't fund legitimate ME/CFS research, but they *will* lump us together with other completely unrelated conditions in an exploratory study on "fatigue"? OK.

 

[Snow Leopard]

https://clinicalstudies.info.nih.gov/ProtocolDetails.aspx?id=20-NR-0003

Researchers hope that ketamine, compared to a drug called midazolam, can reduce fatigue in people with illnesses.

I don't understand why they think this. Both ketamine and midazolam will increase central fatigue. Edit - I think the expected mechanism is an analgesic effect... In the paper mentioned below, the authors speculate about AMPAR activation, by glutamate selectively binding those receptors instead of NDMA receptors (one difference between NDMARs and AMPARs is that the former has ion channels permeable to both calcium and sodium ions, whereas the latter is only permeable by sodium ions). But if we are to entertain that argument, then we also need to consider Kainate receptors and metabotropic glutamate receptors. (and I still don't know how this is supposed to decrease fatigue.) Ketamine is also associated with a transient increase in blood pressure and this may mediate some of the effect.

The principal author wrote a 2015 narrative review discussing potential causes of cancer related fatigue, with the following diagram:

https://pubmed.ncbi.nlm.nih.gov/25975676/

You've probably seen something like this before, only with "Chronic Fatigue Syndrome" at the centre, because the ideas are the same. It's very non-specific and doesn't actually explain anything.

On the trial description page, they cite a general article authored by Sharpe (that if being polite, I can only describe as speculative) and a trial of the effect of ketamine on fatigue in Bipolar patients, also authored by the principal author of the aforementioned trial.
https://pubmed.ncbi.nlm.nih.gov/26807672/
Note, they do discuss that the effect may be biased due to lack of an active placebo (and thus the results are simply reporting biases), hence the use of midazolam in the proposed trial.

The good news is that in the proposed trial, they're not merely relying on questionnaires, but actigraphy as well, so there is less chance of a false positive result due to study biases.

There was also a recent study of Ketamine for MS-related fatigue, with a null primary outcome, but a modest effect on a 28 day outcome:
https://journals.sagepub.com/doi/abs/10.1177/1352458520936226

 

[cfsandmore]

This will count as spending research funding on ME/CFS. NIH is increasing spending on MECFS will be their comment when questioned. This is a big government playing a game.

 

[rvallee]

This will count as spending research funding on ME/CFS. NIH is increasing spending on MECFS will be their comment when questioned. This is a big government playing a game.

True but I'd frame this more as medicine playing a game, this decision is entirely out of the hands of politicians, it's made by medical professionals and scientists. Governments rely on advisers to make decisions, some they leave to the experts. The advice they are getting is this, wasting is a feature, not a bug.

 

[Wonko]

Pain is fatiguing, or at least quite draining.

If, as it may do, ketamine reduces pain, then that would have an effect on energy levels/activity - appearing to help fatigue, when in reality it's done sod all about fatigue, just reduced pain.

I really find it quite mystifying why 'experts' wouldn't know that ketamine can reduce pain, and that pain can cause people to have less oomph, so reducing it would, logically, give them more.

Of course dosage would be critical, take too much and your asleep, or doing naughty things with axes.

 

[Andy]

Merged thread

Sponsoring Institute

National Institute of Nursing Research (NINR)

Background:

Many people experience fatigue as a side effect of their illnesses and treatments. There are no medicines to treat fatigue, but a drug called ketamine has reduced fatigue in depressed people. Researchers hope that ketamine, compared to a drug called midazolam, can reduce fatigue in people with illnesses.

Objective:

To test whether ketamine reduces fatigue in cancer survivors and people with chronic illness.

Eligibility:

Adults between the ages of 18 and 70 who have fatigue and are cancer survivors or have been diagnosed with a chronic illness such as chronic fatigue syndrome and lupus.

https://clinicalstudies.info.nih.gov/ProtocolDetails.aspx?id=20-NR-0003

 

[shak8]

Part of the exclusions for becoming a test subject in this trial:

"4. Current or past psychiatric disorders including medically documented depression with psychosis, bipolar disorder, schizophrenia;

5. Clinically documented post-traumatic stress syndrome and/or traumatic brain injury because of the high risk for ketamine to exacerbate symptoms including hallucinations;"


Ketamine can cause dissociative reactions. I wouldn't take it.

Comparator drug is midazolam, or Versed, basically a benzodiazepam used to knock you out during some minor procedures, or severe anxiety attacks. Impairs memory formation.

 

[Wonko]

For this study, the participant will have an IV, which a needle guides a thin plastic tube (intravenous or IV line) into an arm in their vein.

All of my arms are not in my veins, therefore this procedure would not work on I.

 

[5vforest]

As someone with fatigue who has been prescribed ketamine in various forms…. I am skeptical.

 

[shak8]

From Wikipedia, the only reference to increased energy:

"Ketamine appears not to produce sedation or anaesthesia in snails. Instead, it appears to have an excitatory effect.[151]"

 

[Peter T]

Though this study is not looking at ME as a specified condition, it can not be ruled out that ‘stimulants’ used long term could have harmful effect for people with ME.

If you accept that in ME by definition over exertion can result in a short term negative reaction (PEM) and also potentially a long term deterioration in the underlying condition there would seem to be potential risks in artificially increasing activity levels through drugs. When I was still able to work, I used caffeine and sugar either through carbonated cola drinks or less frequently sweet coffee, a taste for which I have never acquired, to self medicate in order to achieve what was ultimately an unsustainable activity level. I continued this for a number of years after I was forced to give up work to get through unavoidably busier days until I developed an intolerance to both, which now trigger migraines and IBS episodes.

Obviously, I can not be certain that my seeking to self medicate through stimulants did contribute to over exertion triggered deterioration in my condition, it remains a distinct possibility, and is a possibility that anyone seeking to treat ME with chemical stimulants should consider.

 

[Shadrach Loom]

I’d be much more interested in whether psychoactives could do something about pain and hypersensitivity. As @Peter Trewhitt says, masking fatigue is a terrible idea. Masking the constant low-level toxic sensory fizz would be brilliant, though, and a disassociative drug would make marginally as much sense as a depressant.

Unless the idea behind the ket trial is a bit like therapeutic use of LSD, in that the patient is supposed to reframe their beliefs while their brain reboots, which would essentially misrepresent the problem just as CBT does.

 

[Dolphin]

.

 

[Mij]

I'm not sure they got the memo that pwME don't suffer from fatigue.

My experience with caffeine (a stimulant) is that it increases my heart rate and constricts my blood vessels, which in turn makes me dizzy when I stand up.

 

[rvallee]

Disappointing that the first NIH-sponsored trial of a drug is a pointless exercise and obviously grounded on ketamine having some (very weak) promise with depression and thinking it must apply.

Disappointing, but hardly surprising. Medical research is such a broken mess.