Protocol Minirico Mental Intervention and Nicotineamide Riboside Supplementation in Long Covid

Research being done at the University of Oslo with the support of COFFI and the Oslo Fatigue Consortium

MINIRICO - Mental intervention and nicotineamide riboside supplementation in Long COVID

Long COVID, also referred to as post-acute sequela of COVID-19 (PASC), is present in a substantial number of individuals, and treatment for this is warranted.

About the project
MINIRICO is a 2 x 2 factorial randomised control trial on the efficacy and safety of a mental intervention program vs. usual care and nicotinamide riboside (NR) vs. placebo for improving health-related quality of life in the post-COVID-19 condition.

A total of n=310 participants are to be included. Data acquisition is expected completed in 2025. MINIRICO is currently including participants.

Background
Two different hypothetical models of Long COVID suggest attenuated mitochondrial energy production and psychosocial load, respectively, to be key mechanisms in the underlying pathophysiology.

Given the potential importance of metabolic disturbances, dietary supplement by Nicotinamide Riboside (NR, sales name Niagen®) may be beneficial.

Given the potential importance of psychosocial factors, a tailored and personalized Mind-Body Reprocessing Therapy (MBRT) may be beneficial. The MBRT consists of 4 to 6 face-to-face therapist encounters in combination with digital resources.

Method
The study is a randomized controlled trial featuring a 2 x 2 factorial design where MBRT is compared with usual care and NR is compared with placebo. The latter comparison is double blinded.

Eligible participants are individuals (18-70 years) with confirmed Long COVID interferring negatively with daily activities.

A total of 310 participants will be enrolled.
After baseline assessment (T1), the participants will be randomized 1:1 for both treatment comparisons, resulting in four treatment groups:
a) MBRT and NR;
b) usual care and NR;
c) MBRT and placebo;
d) usual care and placebo.

All treatments last for three months, followed by primary endpoint assessment (T2). Total follow-up time is 12 months (T3).

A comprehensive investigational program at all time points includes clinical examination, functional testing (spirometry, autonomic cardiovascular control, neurocognitive functions), sampling of biological specimens (blood) and questionnaire charting (background/demographics, clinical symptoms, psychosocial factors, study events).

Objectives
The primary objective is to determine whether NR 1000 mg twice daily and/or MBRT increase health-related quality of life in individuals with Long COVID compared with care as usual and/or placebo.

Explorative objectives encompass intervention effects on additional cognitive function markers, biological markers (indices of autonomic nervous activity), disability markers (work attendance) and patient symptoms, as well as the exploration of long-term effects, differential subgroup effects, intervention effect mediators and intervention effect predictors.

Primary endpoint:

• The helt subscore from The Medical Outcome Study 36-item short form (SF-36)

Secondary endpoint:

• Markers of inflammation (hsCRP)
  
  
• Cognitive function (digit span test)
  
  
• Cost-effectiveness
  
  
• The patient-reported symptoms fatigue, dyspnoea, and global impression of change in symptoms
  
  
• Function and quality of life

Cooperation

• Professor Torbjørn Omland
• Professor Silje Endresen Reme
• Associate Professor Henrik Børsting Jacobsen
• The COFFI collaborative (external site)

 

Moved posts

Thanks @Midnattsol, we didn't HAVE a thread on this particular study. So it is "Mind-Body Reprocessing Therapy" which they say is a mental intervention, 4-6 sessions with a therapist and digital resources. They assess psychosocial factors and is basically is a CBT like therapy based on psychosomatics i.e. aim to change cognitions and "unhelpful" behaviour

https://www.s4me.info/threads/minir...riboside-supplementation-in-long-covid.41404/

Interestingly it is a completely new form of therapy, there are no scholarly articles on it.

 

I'm really glad to see this trialled, I hope they do a decent job of studying it.

Years ago, some people with ME/CFS tried it (plain old B3 as nicotinamide, though, not this proprietary formulation). Some of us saw significant improvements in quality of life, others saw no benefit at all.

I've been taking it ever since, it was one of the reasons I managed to stay in work for so long. I recently had trouble buying my usual brand and was without it for six or seven weeks; I'd forgotten how bad I feel without it.

 

Interesting.

Not sure if it is a good idea to combine these interventions in the way they do, though, especially with the primary endpoint being a S4-36 scale.

So no matter whether the dietary supplement will show an effect or not, the trial arms with the added therapist-delivered, non-blinded intervention could show a benefit due all kind of biases that aren't controlled for.

Also, not sure about how apt the secondary endpoint are for LC.

Is this a an appropriate test for the kind of cognitive issues people with LC have?

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Also a question for cognitive testing in general, but in particular simple short-time memory tests:

In my case I think e.g. digit span test will show nothing, even when brain-fogged. I'm used to memorize a row of numbers (e.g. phone numbers, library accounts etc.) for a very short period of time by associating a tone [note] to each number, then quietly 'sing' to myself the numbers with a rhythm. Can save and reproduce a row of numbers for some minutes that way if not distracted.

That works automatically. I can write down such rows of numbers on paper or type them into devices I'm used to, depending on how my motor fatigue is at the moment, more or less easily.

That melody trick doesn't help with my working memory / processing speed for other things though -- like being able to type the memorized row of numbers on a keyboard or phone I'm not used to. Or wording, typing and posting a reply here.

Others will apply other memory tools. So how useful are these kind of memory tests in general and for cognitive issues of people with LC or ME/CFS in particular?

 

This one?

https://piccolo-orca-rxh4.squarespace.com/start-her/

 

I think the therapy they are talking about is basically Alan Gordons "Pain Reprocessing Therapy", only rebranded:

https://www.painreprocessingtherapy.com/

 

Wow this is a super weird 'study'.

https://www.med.uio.no/klinmed/engl...ineamide-riboside-supplementation-long-covid/

310 participants in 4 arms. Good grief this must be expensive.

Really going all-in on the foundational biopsychosocial nonsense. Some sham bio bit, but with the usual psychosocial garbage.

 

Looks a lot like the FINE trial, but instead of being told they are fine, the participants tell themselves that.

So, literally The Secret.

 

Knowing these researchers and their history, I'm certain they included this supplement in full knowledge that this is not a plausible treatment and that it is highly unlikely to yield any big effect. They will of course find an effect in the psychosocial treatment arm, and they will conclude with that "these findings support the hypothesis that psychosocial variables are more important than biological factors".

And for the people who haven't seen their former research in the ME/CFS field, they might even sound convincing.

 

@bobbler The digit span test is just one of many cognitive tests in a neuropsychological examination. The tester has to have some training in giving the test but after that it is simple to perform. Remembering the given numbers forward tests short term memory, and backwards, working memory. They start with three random numbers forwards and backwards and then increase by one each time with different numbers each time. The average for adults is 7 but can improve with age.

They say in their study design, above, that participants are going to have "functional testing in neurocognitive functioning". That could be anything but one would hope that each participant would have more than a digit span test.

They have appeared to pick this as their outcome measure. I think this is a bit limited. I am not a psychologist who has specialist training in cognition and statistical analysis of cognitive measures so they would have more of an understanding of the advantages or limitations of using this test alone. But I have done a lot of cognitive assessment when I practised psychiatry. I suppose, being generous, they had to decide on a specific outcome measure and I am hoping when they finish the study and it is peer reviewed that Psychology can question their methods and outcome measures.

They could do the MOCA or MMSE which are very common assessments for cognitive problems and test multiple domains of cognition (attention, concentration, working memory, short and long term memory, visuospatial, naming, reading, commands etc) and are less intensive/time consuming then a full neuropsychological examination. But MOCA's and MMSE are still just screening tools and may not uncover the more subtler problems in LC/ME etc when it is best to do more testing in information processing speed eg Stroop Test and working memory.

The biggest study of cognition and memory in a very large community sampling of people post covid was in the UK as part of the REACT Study
https://www.nejm.org/doi/full/10.1056/NEJMoa2311330
They used 8 tests to give a global cognitive score. The tests are for immediate (short term) memory, spatial working memory, delayed memory, 2D mental manipulation, spatial planning, verbal analogically reasoning, word definitions, information sampling

Other studies on LC have used a variety of cognitive batteries, often online.

More recently they have found pwLC have impaired reaction times which would not be picked up in a digit span test or MOCA/MMSE and would be part of formal neuropsychological testing.
https://www.thelancet.com/action/showPdf?pii=S2589-5370(24)00013-0

I am hoping Psychology will also have something to say about their brand new therapy/mind intervention they call Mind-Body Reprocessing Therapy that so far sounds like positive affirmations and would likely be laughed at by most psychologists/psychiatrists. If only patients could look in the mirror and repeat that "I will recover" and they recovered. We could do away with the all the ills of the world...I had to laugh when they said that MBRT (already an acronym to trot out to make it sound important) might be beneficial. So have they considered the potential harms?

There is no information on it online that I have found so far, so sounds brand new. I am now wondering if they are repurposing some of the NLP/LP techniques and inventing a new alternative psychological therapy (like The Switch, that we unfortunately have here in NZ). It is more in the realm of self-help, pop psychology rather than a real therapy. More like the Secret or the popular "Manifesting" oneself. But I will try and remain openminded (but sceptical) until I know more about it.

 

I don't know how accurately the effect it has on me would show up in their measures. If it works at all, the reduction in pain and fatigue is barn door obvious; there's also a distinctive change in the way muscles feel. Those outcomes are difficult to measure objectively though.

If this trial shows nicotinamide appears to work for some people with long Covid, maybe it would be useful to do the kind of dose response study Jonathan has suggested—especially as it would be tricky to find a workable placebo for anyone who responds as well as I do. I take 350mg once or twice a day, but as I feel awful with none at all, there's likely to be a dose that's too low to work.

The benefits for me (moderate ME/CFS) are:

• Pain relief. It works very well on the distinctive muscle burn in ME/CFS, but not on any other pain.
  
  
• Fatigue. Works very well on the overwhelming heaviness that makes me feel as if I'm wearing a lead suit, but little or no effect on cognitive or physical tiredness after using up the day's capacity.
  
  
• Muscle function. Instead of feeling shaky and unreliable, large muscles spring smoothly into action. It doesn't restore normal function, but does improve it.
  
  
• Rapid muscle fatiguability. Effect is limited, but makes it easier and less painful to walk and dramatically reduced my falls and stumbles.
  
  
• Cognition. Limited effect, could be secondary to pain and fatigue being relieved.
  
  
• Activity capacity. Improved somewhat, but doesn't prevent PEM.
  
  
• Sleep. It doesn't stop PEM-induced insomnia, but switching my daily dose to evening instead of morning has substantially improved my sleep. This is recent and might not persist.

Negatives:

• Skin conditions. Nicotinamide was recommended as a treatment for ME/CFS, which I didn't believe for a second, but I tried it because it's said to have shown effect in managing eczema and contact dermatitis. Turned out it helped with some aspects of ME/CFS but I seem more prone to eczema and contact dermatitis, so I was about as wrong as it's possible to be.

Anything that doesn't prevent PEM isn't a treatment for the underlying problem in ME/CFS, but the specificity is interesting. Why does it relieve pain so effectively, but only one type? Why does it relieve the overwhelming heaviness, but not prevent unusually rapid fatiguability? Why does it stop muscles feeling glitchy and unreliable in a way that's hard to describe but very obvious?

Finally, I wouldn't want to take two grams a day, as in the trial. I've had to buy 500mg capsules when 350mg weren't available, and even that increase is enough to cause headache. They are testing a different formulation, though, I've only used the common-or-garden sort.

 

Google translation from Norwegian to English of the information provided to participants in the Mind-Body Reprocessing Therapy of the study shared in a Norwegian Facebook group
https://piccolo--orca--rxh4-squares...=no&_x_tr_tl=en&_x_tr_hl=en-US&_x_tr_pto=wapp

Of course, if participants in the other treatment/control groups read this and start using the techniques this risks contamination of the result...I wonder if they will acknowledge this in their results (if they become aware of this). I would presume they have told participants not to share the information with other participants.

I am reading through the Minirico (MBRT) modules. I was going to paste them in but as Minirico appears to be a trademarked company, this MBRT protocol is likely to be copyrighted and licensed and I would be breaching this. Also, despite my concerns about the therapy, there is an ethical issue of publishing them while the trial is ongoing.

 

This is pretty much identical to the LP for the most part.

Can't see any concern over copyright as this is generic nonsense.

 

, yes I agree, I am having a wee chuckle that PG found no evidence for the use of brain reprogramming programs in his recent review of the treatments for long covid and here there is a module for "active reprogramming".... To a degree, CBT is a form of reprogramming so what makes them think CBT would work either!

It is more than copyright, I don't know the exact legal term, perhaps intellectual property. When I was working and wanted to get certain psychological scales or manuals on certain psychological therapies I had to buy them. It just occurred to me that Minirico might challenge this website to remove the protocol and that would be a hassle for the moderators.

 

Yeah I assume that a professional would get in trouble for not licensing IP, and they wouldn't have any case objecting to being posted on a public forum, but still best practice to avoid any of this and leave it to be some deep secret they can sell for money. Just like Scientology.

 

I think this article may be related to this although I am not sure because it doesn't mention anything about vitamin B3, it is quite a scary article as it is so disconnected from reality.

https://psykologtidsskriftet.no/fag...ammeringsterapi-mbrt-ny-behandling-long-covid

https://psykologtidsskriftet-no.tra...uto&_x_tr_tl=en&_x_tr_hl=en-US&_x_tr_pto=wapp

 

Yes, that's them. I was on this thread planning to post this myself. I was actually pleasantly surprised as it seemed they have become somewhat less extreme in the psychology-direction. But that in itself really says a lot about them and where they are coming from. I don't know that much about Børsting Jakobsen, but Silje Reme is what I would call downright delusional. For a long time she's been so far divorced from the research on the topics she's been talking about I've been wondering how on earth she hadn't been stopped by colleagues a long time ago. Now she at least seems to be somewhat accepting of the fact that there are biological changes, even though she doesn't give them any weight, before she's seemed to not even acknowledge them in the first place.

Edit: I read the post over here that they've trademarked the Minirico-"method" or whatever you should call it. Does that mean that the potential profits go to the originators (Reme and Børsting Jakobsen, I presume) or the institution/organisation they work at/for? Does anybody know who stands to gain the most - financially speaking - from positive results?