Category: Clinical Trial

FITNET’s Internet-Based Cognitive Behavioural Therapy Is Ineffective and May Impede Natural Recovery in Adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. A Review

Abstract:

The Dutch Fatigue In Teenagers on the interNET (FITNET) study claimed that after 6 months, internet based cognitive behaviour therapy in adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), led to a 63% recovery rate compared to 8% after usual care, and that this was maintained at long term follow up (LTFU).

Our reanalysis shows that their post-hoc definition of recovery included the severely ill, the unblinded trial had no adequate control group and it used lax selection criteria as well as outcomes assessed via questionnaires rather than objective outcomes, further contributing to exaggerated recovery figures. Their decision not to publish the actometer results might suggest that these did not back their recovery claims. Despite these bias creating methodological faults, the trial still found no significant difference in recovery rates (“~60%”) at LTFU, the trial’s primary goal.

This is similar to or worse than the documented 54-94% spontaneous recovery rates within 3-4 years, suggesting that both FITNET and usual care (consisting of cognitive behaviour and graded exercise therapies) are ineffective and might even impede natural recovery in adolescents with ME/CFS. This has implications for the upcoming costly NHS FITNET trial which is a blueprint of the Dutch study, exposing it to similar biases.

Source: Ghatineh S, Vink M. FITNET’s Internet-Based Cognitive Behavioural Therapy Is Ineffective and May Impede Natural Recovery in Adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. A Review. Behav Sci (Basel). 2017 Aug 11;7(3). pii: E52. doi: 10.3390/bs7030052. http://www.mdpi.com/2076-328X/7/3/52 (Full article)

PACE team response shows a disregard for the principles of science

Abstract:

The PACE trial of cognitive behavioural therapy and graded exercise therapy for chronic fatigue syndrome/myalgic encephalomyelitis has raised serious questions about research methodology. An editorial article by Geraghty gives a fair account of the problems involved, if anything understating the case. The response by White et al. fails to address the key design flaw, of an unblinded study with subjective outcome measures, apparently demonstrating a lack of understanding of basic trial design requirements. The failure of the academic community to recognise the weakness of trials of this type suggests that a major overhaul of quality control is needed.

Source: Edwards J. PACE team response shows a disregard for the principles of science. J Health Psychol. 2017 Aug;22(9):1155-1158. doi: 10.1177/1359105317700886. Epub 2017 Mar 28. https://www.ncbi.nlm.nih.gov/pubmed/28805520

Pacing, Conventional Physical Activity and Active Video Games to Increase Physical Activity for Adults with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Protocol for a Pilot Randomized Controlled Trial

Abstract:

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious illness of biological origin characterized by profound physical and cognitive exhaustion and postexertion malaise. Pacing is a common strategy used to manage available energy and complete activities of daily living; yet little research has investigated this as a strategy to increase physical activity levels. Typically, people living with ME/CFS are faced by unique barriers to physical activity participation and are less physically active than healthy peers. As such they are at increased risk of physical inactivity-related health consequences. Active video games may be a feasible and acceptable avenue to deliver physical activity intervention by overcoming many of the reported barriers to participation.

OBJECTIVE: The primary objective of this pilot study is to determine the feasibility and acceptability of active video games to increase physical activity levels of people with ME/CFS. The secondary aims are to explore the preliminary effectiveness of pacing and active video gaming to pacing alone and pacing plus conventional physical activity to increase the physical activity levels of adults with ME/CFS and explore the relationship between physical activity and cumulative inflammatory load (allostatic load).

METHODS: This study will use a mixed method design, with a 3-arm pilot randomized controlled trial, exit interviews, and collection of feasibility and process data. A total of 30 adults with ME/CFS will be randomized to receive either (1) pacing, (2) pacing and conventional physical activity, or (3) pacing and active video gaming. The intervention duration will be 6 months, and participants will be followed up for 6 months postintervention completion. The intervention will be conducted in the participant’s home, and activity intensity will be determined by continuously monitored heart rate and ratings of perceived exertion. Feasibility and acceptability and process data will be collected during and at the end of the intervention. Health-related outcomes (eg, physical activity, blood samples, quality of life, and functioning) will be collected at baseline, end of intervention, and 6 months after intervention completion.

RESULTS: This protocol was developed after 6 months of extensive stakeholder and community consultation. Enrollment began in January 2017; as of publication, 12 participants were enrolled. Baseline testing is scheduled to commence in mid-2017.

CONCLUSIONS: This pilot study will provide essential feasibility and acceptability data which will guide the use of active video games for people with ME/CFS to increase their physical activity levels. Physical activity promotion in this clinical population has been poorly and under-researched, and any exploration of alternative physical activity options for this population is much needed.

TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry: ACTRN12616000285459; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370224 (Archived by WebCite at http://www.webcitation.org/6qgOLhWWf).

Source: Ferrar KE, Smith AE, Davison K. Pacing, Conventional Physical Activity and Active Video Games to Increase Physical Activity for Adults with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Protocol for a Pilot Randomized Controlled Trial. JMIR Res Protoc. 2017 Aug 1;6(8):e117. doi: 10.2196/resprot.7242. http://www.researchprotocols.org/2017/8/e117/ (Full article)

Special issue on the PACE Trial

Abstract:

We are proud that this issue marks a special contribution by the Journal of Health Psychology to the literature concerning interventions to manage adaptation to chronic health problems. The PACE Trial debate reveals deeply embedded differences between critics and investigators. It reveals an unwillingness of the co-principal investigators of the PACE trial to engage in authentic discussion and debate. It leads one to question the wisdom of such a large investment from the public purse (£5 million) on what is a textbook example of a poorly done trial.

Source: David Marks. Special issue on the PACE Trial. Journal of Health Psychology. Vol 22, Issue 9, 2017. http://journals.sagepub.com/doi/full/10.1177/1359105317722370 (Full article)

Influence of morphine and naloxone on pain modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia and controls: a double blind randomized placebo-controlled cross-over study

Abstract:

BACKGROUND: Impaired pain inhibitory and enhanced pain facilitatory mechanisms are repeatedly reported in patients with central sensitization pain. However, the exact effects of frequently prescribed opioids on central pain modulation are still unknown.

METHODS: A randomized, double-blind, placebo-controlled cross-over trial was carried out. Ten CFS/FM patients, 11 RA patients and 20 controls were randomly allocated to the experimental (10 mg morphine or 0.2 mg/ml Naloxone) and placebo (2 ml Aqua) group. Pressure Pain Thresholds (PPTs) and temporal summation at the Trapezius and Quadriceps were assessed by algometry. Conditioned Pain Modulation (CPM) efficacy and Deep Tissue Pain pressure were assessed by adding ischemic occlusion at the opposite upper arm.

RESULTS: Deep Tissue Pain pressure was lower and temporal summation higher in CFS/FM (p=0.002 respectively p=0.010) and RA patients (p=0.011 respectively p=0.047) compared to controls at baseline. Morphine had only a positive effect on PPTs in both patient groups (p time =0.034). Accordingly, PPTs increased after placebo, and no effects on the other pain parameters were objectified. There were no significant effects of naloxone nor nocebo on PPT, Deep Tissue Pain, temporal summation or CPM in the control group.

CONCLUSIONS: This study revealed anti-hyperalgesia effects of morphine in CFS/FM and RA patients. Nevertheless, these effects were comparable to placebo. Besides, neither morphine nor naloxone influenced Deep Tissue Pain, temporal summation or CPM. Therefore, these results suggest that the opioid system is not dominant in (enhanced) bottom-up sensitization (temporal summation) or (impaired) endogenous pain inhibition (CPM) in patients with CFS/FM or RA.

This article is protected by copyright. All rights reserved.

Source: Hermans L, Nijs J, Calders P, De Clerck L, Moorkens G, Hans G, Grosemans S, Roman De Mettelinge T, Tuynman J, Meeus M. Influence of morphine and naloxone on pain modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia and controls: a double blind randomized placebo-controlled cross-over study. Pain Pract. 2017 Jul 19. doi: 10.1111/papr.12613. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28722815

Muscle injections with lidocaine improve resting fatigue and pain in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: Patients with chronic fatigue syndrome (CFS) complain of long-lasting fatigue and pain which are not relieved by rest and worsened by physical exertion. Previous research has implicated metaboreceptors of muscles to play an important role for chronic fatigue and pain. Therefore, we hypothesized that blocking impulse input from deep tissues with intramuscular lidocaine injections would improve not only the pain but also fatigue of CFS patients.

METHODS: In a double-blind, placebo-controlled study, 58 CFS patients received 20 mL of 1% lidocaine (200 mg) or normal saline once into both trapezius and gluteal muscles. Study outcomes included clinical fatigue and pain, depression, and anxiety. In addition, mechanical and heat hyperalgesia were assessed and serum levels of lidocaine were obtained after the injections.

RESULTS: Fatigue ratings of CFS patients decreased significantly more after lidocaine compared to saline injections (p = 0.03). In contrast, muscle injections reduced pain, depression, and anxiety (p < 0.001), but these changes were not statistically different between lidocaine and saline (p > 0.05). Lidocaine injections increased mechanical pain thresholds of CFS patients (p= 0.04) but did not affect their heat hyperalgesia. Importantly, mood changes or lidocaine serum levels did not significantly predict fatigue reductions.

CONCLUSION: These results demonstrate that lidocaine injections reduce clinical fatigue of CFS patients significantly more than placebo, suggesting an important role of peripheral tissues for chronic fatigue. Future investigations will be necessary to evaluate the clinical benefits of such interventions.

Source: Staud R, Kizer T, Robinson ME. Muscle injections with lidocaine improve resting fatigue and pain in patients with chronic fatigue syndrome. J Pain Res. 2017 Jun 26;10:1477-1486. doi: 10.2147/JPR.S139466. ECollection 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499959/ (Full article)

Chronic fatigue syndrome patients have no reason to accept the PACE trial results: Response to Keith J Petrie and John Weinman

Abstract:

Petrie and Weinman urge chronic fatigue syndrome patients to move on from their beliefs about their illness and accept the findings of the PACE trial. This is unreasonable in view of the failure of PACE to achieve evidence of recovery through cognitive behaviour therapy and graded exercise therapy in either self-reports or the objective measure of the 6-minute walking test. Contrary to their suggestion, the Institute of Medicine describes chronic fatigue syndrome not as psychological but as a serious, chronic, systemic disease, with post-exertional malaise as its main feature which inhibits exercise. Linking debate about PACE with intimidation of researchers is unjustifiable and damaging to patients.

Source: Susanna Agardy. Chronic fatigue syndrome patients have no reason to accept the PACE trial results: Response to Keith J Petrie and John Weinman. Journal of Health Psychology. First Published June 27, 2017. http://journals.sagepub.com/doi/10.1177/1359105317715476 (Full article)

Defense of the PACE trial is based on argumentation fallacies

Abstract:

In defense of the PACE trial, Petrie and Weinman employ a series of misleading or fallacious argumentation techniques, including circularity, blaming the victim, bait and switch, non-sequitur, setting up a straw person, guilt by association, red herring, and the parade of horribles. These are described and explained.

Petrie and Weinman (2017) devote fewer than three pages to their defense of the PACE trial, but they nonetheless manage to employ a virtual catalog of misleading or fallacious argumentation techniques. These include circularity, blaming the victim, bait and switch, non-sequitur, setting up a straw person, guilt by association, red herring, and the parade of horribles. Sometimes they engage multiple fallacies in a single paragraph, as I shall explain seriatim.

Source: Steven Lubet. Defense of the PACE trial is based on argumentation fallacies. Journal of Health Psychology. First Published June 14, 2017 Editorial. http://journals.sagepub.com/doi/full/10.1177/1359105317712523 (Full article)

Further commentary on the PACE trial: Biased methods and unreliable outcomes

Abstract:

Geraghty in the year 2016, outlines a range of controversies surrounding publication of results from the PACE trial and discusses a freedom of information case brought by a patient refused access to data from the trial. The PACE authors offer a response, writing ‘Dr Geraghty’s views are based on misunderstandings and misrepresentations of the PACE trial’. This article draws on expert commentaries to further detail the critical methodological failures and biases identified in the PACE trial, which undermine the reliability and credibility of the major findings to emerge from this trial.

Source: Keith J Geraghty. Further commentary on the PACE trial: Biased methods and unreliable outcomes. Journal of Health Psychology, First Published June 14, 2017 Editorial. http://journals.sagepub.com/eprint/iXpCNJk6zd34nFpSy4NK/full (Full article)

Bias, misleading information and lack of respect for alternative views have distorted perceptions of myalgic encephalomyelitis/chronic fatigue syndrome and its treatment

Abstract:

The PACE trial is one of the most recent studies evaluating cognitive behavioural therapy and graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome. These interventions are based on a model which assumes that symptoms are perpetuated by factors such as misguided beliefs and a lack of activity. Our analysis indicates that the researchers have shown significant bias in their accounts of the literature and may also have overstated the effectiveness of the above treatments. We submit that their approach to criticisms undermines the scientific process and is inconsistent with best practice.

Source: Ellen Goudsmit, Sandra Howes. Bias, misleading information and lack of respect for alternative views have distorted perceptions of myalgic encephalomyelitis/chronic fatigue syndrome and its treatment. Jounral of Health Psychology. http://journals.sagepub.com/doi/abs/10.1177/1359105317707216?journalCode=hpqa