Thesis outline:
Given the controversies and uncertainties surrounding these potentially important mediators in CFS, we decided to investigate the role of tryptophan, 5-HT and IGF-1 in CFS in this thesis. Our studies aim to obtain a deeper insight into the pathophysiology of CFS by investigating the efficacy of three biological interventions for CFS.
The effect of Granisetron, a 5-HT3 receptor antagonist, in CFS – In chapter 2 we asked the question whether treatment with a 5-HT3 receptor antagonist is effective in CFS. Studies and clinical observations suggested a role for 5-HT3 receptor antagonism in the treatment of chronic fatigue associated with chronic liver disease and fibromyalgia. The effect of 5-HT3 receptor antagonists in CFS patients had not been investigated in CFS patients before, hence a pilot study was carried out to investigate the effect of Granisetron.
The effect of Ondansetron, a 5-HT3 receptor antagonist, in CFS– In chapter 3 we addressed the same question based on positive findings found in the pilot study described in chapter 2. A randomised double-blind controlled trial was performed. Because granisetron was no longer available at that time, due to a merge of pharmaceutical manufacturer SmithKline Beecham with Glaxo Wellcome, the 5-HT3 antagonist Ondansetron (Zofran) was used to further investigate the effect of 5-HT3 receptor antagonism in CFS.
The effect of Acute Tryptophan Depletion in CFS – Besides intervention with selective serotonin antagonists, we also investigated the effect of Acute Tryptophan Depletion (ATD), a well-known intervention in major depressive disorder The results of a placebo-controlled cross-over ATD study are presented in chapter 4.
Based on the hypothesis that CFS represents a hyperserotonergic state, we used ATD to decrease central serotonin availability, and assessed the effects on fatigue severity, concentration and mood.
The effect of Acclydine in CFS – In chapter 5 we investigated whether CFS patients have lower IGF-1 levels than age, weight and gender matched neighbourhood controls.
Based on the idea that the growth hormone metabolism is disrupted in CFS, De Meirleir in 2001 reported that treatment with Acclydine, a plant-sourced alkaloid, is effective in modifying growth hormone/
IGF-1 status in adult CFS patients and reverts complaints. In 2002, the CFS patient organisation reported in their ‘MEdium Journal’ that the manufacturer of Acclydine had found that 75-80% of CFS patients have a growth hormone deficiency.
Double-blind randomised controlled trials were needed. Acclydine was an expensive treatment and is available on the internet without a prescription. It had been mentioned on the news that Acclydine was recommended for cancer patients with chronic fatigue, and that there were conflicts in Acclydine research. Acclydine was administered to vulnerable patients, but the scientific evidence for efficacy was lacking. The effect of Acclydine, officially a food supplement, was thus evaluated in a randomised controlled clinical trial. We evaluated whether Acclydine is effective in CFS by increasing biologically active IGF-1 levels. Results of a randomised controlled trial are presented in this thesis.
[Comment from M Fluks: Chapter 5 debunks Acclydine therapy. In The Netherlands and Belgium problems arose after Acclydine was sold to PWCs, PWFMs, and Cancer patients (Cancer patients even died due to lack of treatment). Afterwards, things would never be the same: Acclydine therapy marked the beginning of the end of CFS in The Netherlands and Belgium.]
Discussion and future prospects – In chapter 6 I will discuss the main results and implications of the investigations performed, and present recommendations and prospects for future studies.
Chronic Fatigue Syndrome: Targeting Serotonin and Insulin-like Growth Factor, by Gerard Kong Han The. Thesis from Radboud University Nijmegen Medical Centre, 1 Nov 2016
