Category: Clinical Trial

Double-blind randomized controlled trial to assess the efficacy of intravenous gammaglobulin for the management of chronic fatigue syndrome in adolescents

Abstract:

A double blind randomized controlled trial was conducted in 71 adolescents aged 11-18 years. Inclusion in the trial required fulfilment of the diagnostic criteria, (Fukuda et al., 1994).

Three infusions of 1 gm/kg (max 1 litre of 6 gm/100 ml in 10% w/v maltose solution) were given one month apart. The dummy solution was a 10% w/v maltose solution with 1% albumin of equivalent volume for weight. Efficacy was assessed by difference in a mean functional score including school attendance, school work, social activity and physical activity, between baseline, three months and six months after the final infusion.

There was a significant mean functional improvement at the six month follow-up of 70 adolescents with Chronic Fatigue Syndrome of average duration 18 months. There was also a significant improvement for both groups from the beginning of the trial to the six month post infusion follow-up. Adverse effects were common with both solutions but not predictive of response. Neither solution could be identified by recipients.

 

Source: Rowe KS. Double-blind randomized controlled trial to assess the efficacy of intravenous gammaglobulin for the management of chronic fatigue syndrome in adolescents. J Psychiatr Res. 1997 Jan-Feb;31(1):133-47. http://www.ncbi.nlm.nih.gov/pubmed/9201655

 

An open study of the efficacy and adverse effects of moclobemide in patients with the chronic fatigue syndrome

Abstract:

There is a strong association between the chronic fatigue syndrome and both depressive illness and sleep disturbance, but the efficacy of antidepressants is uncertain. We studied the efficacy and adverse effects of moclobemide in patients with chronic fatigue syndrome, stratifying the sample both by co-morbid major depressive illness and by sleep disturbance.

Forty-nine patients with chronic fatigue syndrome were recruited. Patients were given moclobemide up to 600 mg a day for 6 weeks. Four (8%) patients dropped out, three because of adverse effects. Adverse effects were otherwise mild and transient. On analysing the whole sample, there were significant but small reductions in fatigue, depression, anxiety and somatic amplification, as well as a modest overall improvement.

The greatest improvement occurred in those individuals who had a co-morbid major depressive illness, with seven out of 14 (50%) of such individuals rating themselves as “much better” by 6 weeks, compared to six out of 31 (19%) of those who were not depressed (31% difference, 95% CI 1-60%, P = 0.04). Sleep disturbance had no effect on outcome.

Moclobemide may be indicated in patients with chronic fatigue syndrome and a co-morbid major depressive disorder. A randomized, placebo-controlled trial is needed to confirm this. These results do not support moclobemide as an effective treatment of chronic fatigue syndrome in the absence of a major depressive disorder.

 

Source: White PD, Cleary KJ. An open study of the efficacy and adverse effects of moclobemide in patients with the chronic fatigue syndrome. Int Clin Psychopharmacol. 1997 Jan;12(1):47-52. http://www.ncbi.nlm.nih.gov/pubmed/9179634

 

Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome

Abstract:

Carnitine is essential for mitochondrial energy production. Disturbance in mitochondrial function may contribute to or cause the fatigue seen inChronic Fatigue Syndrome (CFS) patients.

Previous investigations have reported decreased carnitine levels in CFS. Orally administered L-carnitine is an effective medicine in treating the fatigue seen in a number of chronic neurologic diseases. Amantadine is one of the most effective medicines for treating the fatigue seen in multiple sclerosis patients. Isolated reports suggest that it may also be effective in treating CFS patients. Formal investigations of the use of L-carnitine and amantadine for treating CFS have not been previously reported.

We treated 30 CFS patients in a crossover design comparing L-carnitine and amantadine. Each medicine was given for 2 months, with a 2-week washout period between medicines. L-Carnitine or amantadine was alternately assigned as first medicine.

Amantadine was poorly tolerated by the CFS patients. Only 15 were able to complete 8 weeks of treatment, the others had to stop taking the medicine due to side effects. In those individuals who completed 8 weeks of treatment, there was no statistically significant difference in any of the clinical parameters that were followed.

However, with L-carnitine we found statistically significant clinical improvement in 12 of the 18 studied parameters after 8 weeks of treatment. None of the clinical parameters showed any deterioration. The greatest improvement took place between 4 and 8 weeks of L-carnitine treatment. Only 1 patient was unable to complete 8 weeks of treatment due to diarrhea.

L-Carnitine is a safe and very well tolerated medicine which improves the clinical status of CFS patients. In this study we also analyzed clinical and laboratory correlates of CFS symptomatology and improvement parameters.

 

Source: Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome. Neuropsychobiology. 1997;35(1):16-23. http://www.ncbi.nlm.nih.gov/pubmed/9018019

 

The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). II. Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment

Abstract:

This study is a counterpart of the pilot study on the clinical management of chronic fatigue syndrome (CFS) by the combined use of the old (annex-free) and the new (dehydro-epiandrosterone- annexed) vitamin C infusion treatments with and without oral intake of erythromycin and chloramphenicol. We were motivated to start this clinical study by 2 reasons:

i) we have made a success in the clinical management of autoimmune disease and allergy by use of the old megadose vitamin C infusion treatment, and we therefore took up CFS as a good candidate for vitamin C infusion treatment;

ii) In 1995, we received a total of 313 chronic pneumonia patients whose clinical course showed a good fitness to the criteria of CFS.

We assessed the nature of the disease by investigating the clinicoepidemiological aspect of our patients on the one hand and the response of the disease to both the old and new vitamin C infusion treatments with and without the use of 2 antibiotics on the other hand. Results are summarized as follows:

a) the analysis of the medical records of our outpatients revealed that chronic type pneumonia epidemic in Nagoya Japan, with its onset of January 1995, showed no sign of its extinction by the end of May 1996. The patient population contained no patients under 15 years of age, and showed a distinct female predominance in the patient number (207 females versus 106 males). In 1995, we also experienced a simple cold epidemic with its onset of January 1995 (162 males and 224 females). The majority of simple cold patients were under 25 years of age in both sexes.

b) A chronic type pneumonia patient was distinguished from a simple cold patient in 2 respects: firstly the former required prolonged medical care (over 1 month) resulting in an incomplete cure and return to medical care upon the recurrence of disease, whereas the latter required short-term medical care (mostly within 1 week) ending up with complete cure. Secondly, the former required the long term use of 2 antibiotics (erythromycin and chloramphenicol) together with regular practice of the old and new vitamin C infusion treatments for disease control, whereas the latter recovered from the disease after the short time use of a set of conventional cold remedies.

c) The clinical manifestations of our chronic pneumonia patients showed good fitness to the criteria of CFS.

d) CFS was distinguished from autoimmune disease-allergy complex by the method of clinical control: the former required the long-term use of 2 antibiotics together with regular practice of the old and new vitamin C infusion treatments, whereas the latter was controllable by the single use of the old vitamin C infusion treatment.

e) The combined use of the old and new vitamin C infusion treatments rather than the single use of the old vitamin C infusion treatment was more effective for the control of CFS-a finding which suggests that deficient activities of both endogenous glucocorticoid and endogenous androgen in a CFS patient are somehow related to the genesis and further development of CFS.

f) Evidence was available to indicate that the sole use of the new vitamin C infusion treatment may induce a state of gonadal steroid excess together with various other problems in the recipient. The maintenance of a good balance between the old vitamin C infusion set (glucocorticoid-inducer) and the new vitamin C infusion set (inducer of both glucocorticoid and gonadal steroids) in their use was of prime importance for the successful control of CFS.

g) The historical significance of CFS epidemic in 1995, and in Nagoya-Japan, is discussed in the light of the new infection concept.

 

Source: Kodama M, Kodama T, Murakami M. The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). II. Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment. In Vivo. 1996 Nov-Dec;10(6):585-96. http://www.ncbi.nlm.nih.gov/pubmed/8986468

 

The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). I. A Pilot study of the new vitamin C infusion treatment with a volunteer CFS patient

Abstract:

A series of publications from our laboratory have indicated that the practice of megadose vitamin C drip infusion treatment enhanced the activity of endogenous glucocorticoids in such a way as to improve the clinical course of allergy and autoimmune disease-a disease entity that is known to respond to the therapeutic effect of glucocorticoids. The present paper represents an extention of our vitamin C studies, and intends to investigate the problem whether or not chronic fatigue syndrome (CFS), an acquired immunodeficiency disease, can also be counted as one of the candidate diseases for the vitamin C infusion treatment.

We prepared two kinds of vitamin C infusion sets for the clinical use: the dehydroepiandrosterone-annexed vitamin C infusion set (the new set) and the annex-free vitamin C infusion set (the old set). The new set was expected to enhance the endogenous activities of both glucocorticoids and gonadal steroids.

We followed the clinical course of a male CFS patient using the old and new vitamin C infusion sets, and with and without the oral intake of erythromycin and chloramphenico. Results obtained are as follows:

a) the observation period of a study subject covered a period of August 1995 to May 1996. Combination of pneumonia signs and dermatomyositis signs marked the onset of his CFS.

b) Old infusion treatment together with the short term antibiotics treatment was found effective for the control of pneumonia in the first stage of the disease (from August to October, 1995).

c) Signs of pneumonia recurrence gradually became eminent in the second stage of disease (from November, 1995, to January, 1996) in spite of the moderate frequency of the old treatment together with stepwise prolongation of the antibiotics treatment.

d) The alternate practice of the old and new infusion treatments together with the long-term antibiotics treatment, as conducted in the 3rd stage of disease (from February to May, 1996) led to substantial extinction of pneumonia signs (leucocytosis, tachycardia etc).

e) The practice of the new infusion treatment markedly increased the excretion of both 17-ketosteroids and 17-hydroxycorticosteroids in the urine. Evidence was also available to indicate that the dehydroepiandrosterone annex was converted to testosterone, which in turn made a contribution to the control of CFS.

f) The immunological survey of lymphocyte subsets including NK cell percent failed to find a coherent change in a study subject with CFS.

In conclusion, the above results could be taken as evidence to indicate that the new vitamin C infusion treatment effectuates the clinical control of CFS by fortifying the endogenous activities of both cortisol and testosterone. The significance of parallelism between pulmonary infection and CFS, as observed in the clinical course of the test subject, was discussed in the light of the focal infection theory of nephritis.

 

Source: Kodama M, Kodama T, Murakami M. The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). I. A Pilot study of the new vitamin C infusion treatment with a volunteer CFS patient. In Vivo. 1996 Nov-Dec;10(6):575-84. http://www.ncbi.nlm.nih.gov/pubmed/8986467

 

N of 1 trials. Managing patients with chronic fatigue syndrome: two case reports

Abstract:

Chronic fatigue syndrome is a heterogeneous condition with as proves effective treatment. I present two case reports in which N of 1 trials helped me make management decisions. High-dose vitamin B12 injections were ineffective in one case; nimodipine was very effective in the other case.

 

Source: Wiebe E. N of 1 trials. Managing patients with chronic fatigue syndrome: two case reports. Can Fam Physician. 1996 Nov;42:2214-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2146911/ (Full article)

 

Randomized, double blind, controlled placebo-phase in trial of low dose phenelzine in the chronic fatigue syndrome

Abstract:

Because of the striking similarity of the clinical manifestations produced by use of the drug reserpine and seen in patients with the chronic fatigue syndrome (CFS), we theorized that CFS was a disorder of reduced central sympathetic drive. Because of the pharmacology of control of this central sympathetic system, we further postulated that CFS symptoms would respond quickly to low dose treatment with a monamine oxidase inhibitor. To test these hypotheses, we designed a randomized, double blind placebo controlled study using phenelzine.

No patient in the trial had a diagnosis of lifetime or current psychiatric disorder and none had depressed mood in the range of clinically depressed patients on a paper and pencil test of depression. Patients in the placebo group received placebo for 6 weeks while those in the drug treatment group were treated in three 2-week segments-placebo, 15 mg phenelzine every other day, and then 15 mg daily. This treatment regimen produced a significant pattern of improvement compared to worsening in 20 self report vehicles of CFS symptoms, illness severity, mood or functional status.

Thus the data support our hypothesis of reduced sympathetic drive, although an alternative hypothesis of pain alleviation is also possible. The study design also allowed us to evaluate patients for a placebo effect: no evidence for this was found, suggesting that CFS is not an illness due to patients’ being overly suggestible.

 

Source: Natelson BH, Cheu J, Pareja J, Ellis SP, Policastro T, Findley TW. Randomized, double blind, controlled placebo-phase in trial of low dose phenelzine in the chronic fatigue syndrome. Psychopharmacology (Berl). 1996 Apr;124(3):226-30. http://www.ncbi.nlm.nih.gov/pubmed/8740043

 

Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome

Abstract:

BACKGROUND: No somatic treatment has been found to be effective for chronic fatigue syndrome (CFS). Antidepressant therapy is commonly used. Fluoxetine is recommended in preference to tricyclic agents because it has fewer sedative and autonomic nervous system effects. However, there have been no randomised, placebo-controlled, double-blind studies showing the effectiveness of antidepressant therapy in CFS. We have carried out such a study to assess the effect of fluoxetine in depressed and non-depressed CFS patients.

METHODS: In this randomised, double-blind study, we recruited 44 patients to the depressed CFS group, and 52 to the non-depressed CFS group. In each group participants were randomly assigned to receive either fluoxetine (20 mg once daily) or placebo for 8 weeks. The effect of fluoxetine was assessed by questionnaires, self-observation lists, standard neuropsychological tests, and a motion-sensing device (Actometer), which were applied on the day treatment started and on the last day.

FINDINGS: The two groups were well matched in terms of age, sex distribution, employment and marital status, and duration of CFS. There were no significant differences between the placebo and fluoxetine-treated groups in the change during the 8-week treatment period for any dimension of CFS. There was no change in subjective assessments of fatigue, severity of depression, functional impairment, sleep disturbances, neuropsychological function, cognitions, or physical activity in the depressed or the non-depressed subgroup.

INTERPRETATION: Fluoxetine in a 20 mg daily dose does not have a beneficial effect on any characteristic of CFS. The lack of effect of fluoxetine on depressive symptoms in CFS suggests that processes underlying the presentation of depressive symptoms in CFS may differ from those in patients with major depressive disorder.

 

Source: Vercoulen JH, Swanink CM, Zitman FG, Vreden SG, Hoofs MP, Fennis JF, Galama JM, van der Meer JW, Bleijenberg G. Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome. Lancet. 1996 Mar 30;347(9005):858-61. http://www.ncbi.nlm.nih.gov/pubmed/8622391

 

Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial

Abstract:

OBJECTIVE: To evaluate the acceptability and efficacy of adding cognitive behaviour therapy to the medical care of patients presenting with thechronic fatigue syndrome.

DESIGN: Randomised controlled trial with final assessment at 12 months.

SETTING: An infectious diseases outpatient clinic.

SUBJECTS: 60 consecutively referred patients meeting consensus criteria for the chronic fatigue syndrome.

INTERVENTIONS: Medical care comprised assessment, advice, and follow up in general practice. Patients who received cognitive behaviour therapy were offered 16 individual weekly sessions in addition to their medical care.

MAIN OUTCOME MEASURES: The proportions of patients (a) who achieved normal daily functioning (Karnofsky score 80 or more) and (b) who achieved a clinically significant improvement in functioning (change in Karnofsky score 10 points or more) by 12 months after randomisation.

RESULTS: Only two eligible patients refused to participate. All randomised patients completed treatment. An intention to treat analysis showed that 73% (22/30) of recipients of cognitive behaviour therapy achieved a satisfactory outcome as compared with 27% (8/30) of patients who were given only medical care (difference 47 percentage points; 95% confidence interval 24 to 69). Similar differences were observed in subsidiary outcome measures. The improvement in disability among patients given cognitive behaviour therapy continued after completion of therapy. Illness beliefs and coping behaviour previously associated with a poor outcome changed more with cognitive behaviour therapy than with medical care alone.

CONCLUSION: Adding cognitive behaviour therapy to the medical care of patients with the chronic fatigue syndrome is acceptable to patients and leads to a sustained reduction in functional impairment.

Comment in:

Cognitive behaviour therapy for the chronic fatigue syndrome. Good general care may offer as much benefit as cognitive behaviour therapy. [BMJ. 1996]

Cognitive behaviour therapy for the chronic fatigue syndrome. Patients were not representative of all patients with the syndrome. [BMJ. 1996]

Cognitive behaviour therapy for the chronic fatigue syndrome. Cognitive behavior therapy should be compared with placebo treatments. [BMJ. 1996]

ACP J Club. 1996 May-Jun;124(3):71.

Cognitive behaviour therapy for the chronic fatigue syndrome. Use an interdisciplinary approach. [BMJ. 1996]

Cognitive behaviour therapy for the chronic fatigue syndrome. Patients’ beliefs about their illness were probably not a major factor. [BMJ. 1996]

Cognitive behaviour therapy for the chronic fatigue syndrome. Evening primrose oil and magnesium have been shown to be effective. [BMJ. 1996]

Cognitive behaviour therapy for the chronic fatigue syndrome. Essential elements of the treatment must be identified. [BMJ. 1996]

 

Source: Sharpe M, Hawton K, Simkin S, Surawy C, Hackmann A, Klimes I, Peto T, Warrell D, Seagroatt V. Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. BMJ. 1996 Jan 6;312(7022):22-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2349693/

Note: You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2349693/pdf/bmj00523-0026.pdf

 

 

Lessons from a pilot study of transfer factor in chronic fatigue syndrome

Abstract:

Transfer Factor (TF) was used in a placebo controlled pilot study of 20 patients with chronic fatigue syndrome (CFS). Efficacy of the treatment was evaluated by clinical monitoring and testing for antibodies to Epstein-Barr virus (EBV) and human herpes virus-6 (HHV-6). Of the 20 patients in the placebo-controlled trial, improvement was observed in 12 patients, generally within 3-6 weeks of beginning treatment. Herpes virus serology seldom correlated with clinical response. This study provided experience with oral TF, useful in designing a larger placebo-controlled clinical trial.

 

Source: De Vinci C, Levine PH, Pizza G, Fudenberg HH, Orens P, Pearson G, Viza D. Lessons from a pilot study of transfer factor in chronic fatigue syndrome. Biotherapy. 1996;9(1-3):87-90. http://www.ncbi.nlm.nih.gov/pubmed/8993764