Clinical Trials Ending This Year or Late Last Year
The coronavirus pandemic stopped everything for quite a while but the clinical trials which survived the pandemic probably started up again quite some time ago. All we have to go by, though, are the stated completion times listed in the https://www.clinicaltrials.gov/ database which provides information on clinical trials in over 200 countries. That said, check out the clinical trials for ME/CFS and fibromyalgia that were projected to end in the last half of last year or this year. (A few trials not listed for ME/CFS are included as well.)
Plus check out possible game-changers: trials big enough to quickly lead to FDA approval or to quickly produce follow-up trials for FDA approval, or which could lead the medical profession to adopt new treatment options. These trials are highlighted.
Chronic Fatigue Syndrome (ME/CFS)
This 50-person, placebo-controlled, double-blinded study by David Systrom was projected to have been completed last year. This is a trial which, because it’s employing a readily available and well-known drug could, if successful, rather quickly produce significant results for the ME/CFS community.
Systrom believes Mestinon may be causing the veins in a subset of ME/CFS/FM patients to narrow, thus propelling blood back up to the heart and providing the muscles, brain, etc. with the blood they’ve been missing. Retrospective studies suggest Mestinon may be able to improve oxygen uptake, end-tidal carbon dioxide levels, and ventilatory efficiency.
This study is going to do more than assess symptom responses, though. It will, using Systrom’s blood tests and his invasive exercise equipment, measure lactate levels, oxygen uptake by the muscles, output from the heart, heart rate, carbon dioxide production and 7 more cardiovascular factors.
Furthermore, the study was extended by a 2020 CDMRP grant to Dr. Rosa Maria Pari Ñaña to identify which patients will likely benefit from Mestinon..The study isn’t large enough to produce FDA approval but a positive result should certainly help doctors try this old drug in their ME/CFS patients.
Oral Rehydration/Saline – (this study may have already been completed). A recent oral rehydration study found that off-the-shelf oral rehydration salts were as effective as saline IVs in ME/CFS and POTS.
Solriamfetol – a most interesting narcolepsy drug is being trialed in ME/CFS. One doctor told me that in his experience people with ME/CFS have a sleep-wake instability similar to narcolepsy and that he, himself, responded very well to a drug (sodium oxybate) prescribed for narcolepsy.
Solriamfetol is a norepinephrine–dopamine reuptake inhibitor (NDRI) that increases the availability of dopamine and norepinephrine. It was FDA-approved recently (March 2019) for treating excessive sleepiness in narcolepsy and residual sleepiness in people with obstructive sleep apnea. It’s believed to be safer than traditional stimulants. It’s interesting that the leader of this study, Joel Young MD, so quickly jumped on the opportunity to test this new drug. Young is a psychiatrist who firmly believes ME/CFS is a physical illness, has written a book on it, and employs an interesting treatment approach that includes both long-acting stimulants and meditation. (!).
- VIRTUAL SFCAMINA – combines a multicomponent approach based on Pain Neuroscience Education (PNE), therapeutic exercise, Cognitive Behavioral Therapy (CBT), and Mindfulness training.
- Yan Nian Jiu Zhuan Fa – Chinese massage and behavioral approach
ME/CFS Trials Not in the Clinical Trials Database
Nancy Klimas’s “Moonshot Trial”
Called by Nancy Klimas her “moonshot trial” – as in she’s reaching for the moon – this trial is attempting to reset and return ME/CFS patients’ system back to normal. This etanercept/mifepristone trial was based on extensive computer modeling which was then validated in a Gulf War Illness (GWI) mouse model. (A GWI trial has been underway as well.)
This trial is particularly intriguing as Dr. Klimas’s research indicates that GIWI and ME/CFS are quite different diseases but her modeling work suggests this drug combination – etanercept administered earlier to combat neuroinflammation and mifepristone later to reset the HPA – should work in both illnesses.
This trial was fully (privately) funded and was about to start when the pandemic hit. Dr. Klimas reported last spring that the trial was “back in the saddle”. No telling when it was supposed to wind up but as it was a small study 2022 seemed likely.
This trial certainly has the potential to be a “game-changer” but my guess is that it’s probably too small for many doctors to take on trying these drugs.
Repetitive Transcranial Magnetic Stimulation – this small but innovative pilot UCLA trial is going to stimulate two parts of the brain (limbic system/prefrontal cortex) simultaneously. Funded by the Solve ME Initiative in the first part of 2021 was reportedly going to get underway quickly, and could if it wasn’t thwarted by the pandemic, have results shortly
Suramin Trial – Bob Naviaux – It’s been reported that this trial has been funded and will begin this year. Ron Davis has expressed hope that it will provide some answers.
Inspiratory Muscle Training – I’m not sure when this small study funded by Solve ME will end up, but its a good one to keep an eye on given all the breathing problems found in ME/CFS.
A Ketamine Revolution?
Formerly used as an anesthetic drug, ketamine has produced some eye-opening results in both depression and pain. Two fibromyalgia studies are underway or have recently started:
This big 210-person Belgium study certainly seems to have the heft to change things in Europe. The U.S. is another matter but a win here would surely entice U.S. firms to take a look.
- Comparison of Ketamine and Esketamine (KESK-FIQ) – this is a smaller U.S. study.
Learn much more about ketamine and fibromyalgia here
*Possible Game-Changer Fibromyalgia Outcome Research Trial Evaluating Synergistic Suppression of HSV-1 (FORTRESS)
Dr. Pridgen Does It!
However, it turns out it’s been gratifying to see Dr. Pridgen’s work over the past 10 years pay off in this big 460-person, multicenter, antiviral trial. It’s slated to end in June of this year. The fact that Pridgen was able to get an antiviral trial underway in a disease that’s never shown the slightest interest in pathogens is astonishing in itself. This is one of the big FM trials which, if successful, could ultimately result in FDA approval – and a dramatic reassessment of the disease itself.
Check out a rather astonishing recovery story.
A Study to Evaluate Lu AG06466 in Participants with Fibromyalgia – this intriguing drug inhibits the enzyme that breaks down endocannabinoids – thus making this feel-good compound more available. An inhibition of the body’s own cannabinoid production has been proposed for FM. The drug may also reduce neuroinflammation. (An endogenous opioid assessment study is also underway in FM.)
Learn more about endocannabinoids and FM here:
The Effect of Minocycline and N-acetylcysteine for the Treatment of Fibromyalgia Minocycline has stirred interest as a possible anti-neuroinflammatory and NAC is a potent antioxidant that can make it to the brain. Some evidence suggests that using them together may produce synergistic effects. Shungu’s preliminary NAC findings in ME/CFS were promising and a NAC treatment trial is underway in ME/CFS.
This and Pridgen’s trial may be the trials to watch out for. This big Phase II trial, if successful, would quickly be followed by a Phase III trial, setting up this drug for FDA approval. NYX-2925 by Aptinyx is notable in that it could help with both sleep and pain in FM. The trial was projected to end in June 2022.
Symptom improvements by this drug have been correlated with reductions in the excitatory and sometimes neurotoxic compound glutamate in two key pain processing areas in the brain (insula, anterior cingulate). (Studies have highlighted those brain areas in ME/CFS as well.) NYX-2925 is also intriguing in that it apparently provides a kind of neuroplastic boost by enhancing synaptic plasticity.
Aptinyx, its manufacturer, appears to be quite high on the drug and expects it to be helpful in other chronic pain conditions characterized by central sensitization. (That would, of course, include ME/CFS).
It’s been over ten years since the last drug was FDA approved for FM. Hopefully, Aptinyx breaks the string of bad luck visited upon several recent major efforts (Mirogabalin, TNX-102) to bring a new drug to market for FM. Speaking of bad luck…
*Possible Game Changer – Will Tonix TNX 102’s Rough, Rough, Ride End Well?
This drug is down right now but this drug has been down before and could emerge to be a game-changer. It’s had lots of study in lots of FM patients and a good result could put it over the top.
That said, no potential FM drug has had a more rollercoaster journey than Tonix’s TNX-102 SL drug. Excited to add a sleep and pain improving drug to the FM drug basket, Tonix started TNX-102’s phase III trial in FM before it’s phase II trial had ended.
That trial didn’t make its endpoints (wiping out $70 million in stock valuations) but then after the drug worked in PTSD at a higher dose, the company re-evaluated its data and began another larger phase III drug trial only to suspend it mid-trial in July of last year after an interim analysis suggested that it would make not make its primary endpoints.
Then in November, the company reported positive results from the truncated FM trial stating that it did meet its primary endpoint (reducing daily pain) and showed “activity” with regard to improved sleep, reduced fatigue and functionality.
Tonix doesn’t know what to do regarding their flagship drug right now. Two similar studies have produced different results and they don’t know why. They expect to have the analysis done sometime early this year. Meanwhile, one media outlet reported another Phase III trial – the third one for this drug (!) is expected this year.
The company reported it was considering tryingTNX-102 out in long COVID.
It’s really good to see anti-CGRP based drugs developed to treat migraines – a common comorbid condition in both FM and ME/CFS – get a shot at fibromyalgia as well. Check out a story of an FM patient who found that both her migraines and FM got better on one of these drugs.
*Possible Game Changer –A Study to Test the Effectiveness and Safety of Fremanezumab on Patients With Fibromyalgia -.
The size of this trial (220 patients) indicates that its drug manufacturer (Teva) has high hopes for this drug. While it’s not clear that this one trial would be enough for drug approval a positive result would mean a quick turnaround trial plus it would surely encourage other anti-CGRP drug companies to quickly jump into the lucrative fibromyalgia drug market. This project was expected to end in March 2022.
- Anti-CGRP for Inflammation and Pain Modulation in Small Fiber Neuropathy/Fibromyalgia – small study using Galcanezumab
- Pyridostigmine bromide (Mestinon) – this study by David Systrom was projected to have been completed last year (see ME/CFS section)
Magnetic Stimulation of the Brain
The rapidly evolving magnetic stimulation field holds the promise of safely and effectively turning down overactive parts of the brain involved in pain processing and/or ramping up parts of the brain involved in executive functioning
- Repetitive Transcranial Magnetic Stimulation of Relief of Fibromyalgia Pain (TMSFFI) – due to end late last year
- Montage of HTDCS in Psycho-cognitive Functions in FM (HFTDCS)– home based anodic transcranial direct current stimulation (tDCS) trial
- Effect of Hypnosis Combined With Tdcs on Pain Perception and Cortical Excitability in Fibromyalgia – hypnosis + transcranial direct-current stimulation…Interesting!
PEA (palmitoylethanolamide) – It’s great to see this anti-inflammatory and neuroprotective product being trialed in FM. PEA is a natural substance that’s produced on demand in areas of local inflammation. It appears to be able to tamp down inflammation and microglial and mast cell activation.
PEA has been described as a case study of the medical research establishment ignoring possibly effective treatments that it doesn’t understand. It apparently took a Nobel Laureate to spark interest in the drug.
Many European studies have apparently assessed PEA’s effectiveness in pain but this is the first FM study that I know of to do so. Find out more about PEA.
- Micronized and Ultramicronized Palmitoylethanolamide in Fibromyalgia Patients – The 60 person Italian study was projected to end up last year.
- Effect of an Amino-Acid-Based Blend on Human Growth Hormone (hGH) and Fibromyalgia (FM) Symptoms – 100-person study.
- Treatment of Fibromyalgia and CFS With Ribose, Ashwagandha, Rhodiola, Licorice, Schisandra and Green Tea Extract – projected to end summer of last year.
Physio and Heat Therapy
Dr. Ginerva Liptan has said that massage is amongst the most effective treatments for her patients.
- Bowen Therapy for Pain Management in FM – Bowen Therapy uses specific sequences of gentle cross-fiber moves over muscles, tendons, ligaments, and fascia to stimulate or improve the flow of blood and lymph, and thus activate the body’s healing mechanisms that enhances tissue repair. As a result, it can lessen pain and tension, restore more optimal body function, and subsequently alleviate emotional and psychological stress associated with the pain. Would this be helpful for the muscoskeletal problems Dr. Rowe finds in ME/CFS?
- Effects of Mobilization and Perceptive Rehabilitation on Patients with Fibromyalgia Syndrome (“the Cone Trial”) – the tool consisted of cones made from a latex material which were placed under the patient’s back during treatment sessions. These cones were intended to improve tactile response and proprioception, the so-called perceptual surface.
- Effectiveness of Manual Lymphatic Drainage in Patients With Fibromyalgia (EMLDIPWF) – projected to have ended last year. Check out a video on lymphatic drainage.
- Kinesio Taping and Inhibitory Treatment Techniques – is “a therapeutic taping technique which alleviates pain and facilitates lymphatic drainage by microscopically lifting the skin. This lifting affect forms convolutions in the skin increasing interstitial space and allowing for decreased inflammation in the affected area”
- Heat Therapy for Fibromyalgia – involves getting dunked in hot water
- POLD manual physiotherapy
Coordinated pulses of light, wearable brain-sensing devices, photomodulation, etc. – it was surprising to see the creative attempts underway that seek to gently alter brain functioning in FM.
- Efficacy of Sana Treatment in Fibromyalgia – Sana is a mask that provides coordinated pulses of light (through closed eyelids) and sound at various frequencies. Interesting! Projected to have ended in Sept. of last year.
- Remote Gamified Sensory Perceptual Training for Patients with Fibromyalgia: a Feasibility Trial – includes a smartphone app and two vibrational devices.This study was projected to have ended last year
- Evaluating Mindfulness-Based Interventions with New Fibromyalgia Patients – combining a “wearable brain-sensing device” and mindfulness training.
- Effects of Photobiomodulation in a Population Suffering from Fibromyalgia – uses red and near-infrared light to penetrate through the skull and into the brain cells. Believed to increase brain blood flows, mental clarity, energy.
- Acupuncture for Fibromyalgia Syndrome
- Auriculotherapy Treatment in Fibromyalgia (Fib-Auric) – needling points in the ear
- Comparison of Focused ESWT by Frequency for Patients with Myofascial Pain Syndrome- extracorporeal shockwave therapy
- Except for the big iCBT study all these studies hail from Europe (Spain, Turkey) or Israel
- Efficacy of Psychological Therapy in Chronic Pain and Fibromyalgia (DOLORTRATPSI)
- Group psychotherapy
- An Emotional Regulation Brief Procedure (PbRE) for Fibromyalgia Using ICT’s (PbRE
- Pain Neuroscience Education in Patients With Fibromyalgia
- Effectiveness Pain Neuroscience Education In The Executive Functions In Patients With Fibromyalgia (PNE)
- Impact of Post-Traumatic Stress Disorder Treatment by Reconsolidation Therapy on Fibromyalgia Syndrome (PTSD-FMS) – people with FM and PTSD take propanolol and then engage in reconsolidation blockade therapy.
- Sleep and Pain Interventions in Women With Fibromyalgia (SPIN-II) – huge 1300 person NIH funded iCBT/ sleep hygiene in FM women with insomnia
Exercise and Movement Therapies
Exercise has been a major theme of FM clinical trials for a long time.
- Ba-Duan-Jin therapy (QiJong) – 2 studies
- Effectiveness of VIRTUAL FIBROWALK STUDY – VIRTUAL FIBROWALK combines multicomponent approach based on Pain Neuroscience Education (PNE), therapeutic exercise, Cognitive Behavioural Therapy (CBT) and Mindfulness training.
- The Effect of Group Exercise and Thetahealing on Pain and Quality of Life in Patients With Fibromyalgia
- Comparative Study About the Effect of Aquatic Therapy vs Land-based Therapy in Women With Fibromyalgia
- Telehealth Stretching Exercise Program for Women With Fibromyalgia During the Covid-19 Pandemic
- The Effect of Tai Chi in Treating Fibromyalgia
- Aerobic Exercises and Postural Stabilization Exercises in Fibromyalgia Syndrome
- Neurohormonal Benefits of Exercise in Fibromyalgia and PTSD
The Looking Forward to 2022 Series
Check out Pt. I of Health Rising’s “Looking Forward to 2022 Series: The Long COVID Research Boom