ISRCTN - ISRCTN07518149: Pilot study to investigate if reducing serotonin levels in patients with chronic fatigue syndrome is effective.

Plain English Summary

Background and study aims
Chronic fatigue syndrome (CFS) is still an enigmatic disorder. It is complex and has a huge impact on the lives of those affected. Full recovery without treatment is rare. We still do not have a somatic explanation for the fatigue is lacking. Enhanced serotonin metabolism could play an important role in CFS. This study investigates the effect of reducing serotonin levels in patients with CFS.

Who can participate?
Female CFS-patients between 18 and 40 years, fulfilling the US Center for Disease Control and Prevention criteria can participate. Exclusion criteria are: pregnancy, previous or current participation in CFS-research, use psychotropic medication (antidepressants, sleep medication) in the last month. Vegetarians and lactating women are excluded as well.

What does the study involve?
The effect on fatigue severity, concentration and mood will be assessed. Serotonin levels can temporarily be reduced by taking an amino-acid drink without tryptophan. Tryptophan is a precursor of serotonin. There are two test-days, one week apart. On each test day patients will receive an amino acid drink. Patients will receive a dummy amino-acid drink and on the other test day patients will receive the real amino acid drink that will reduce serotonin levels. At the end of the study we will compare the effects of the real and the dummy drinks.

What are the possible benefits and risks of participating?
The effect of lowering serotonin levels in CFS patients is under investigation. It is not clear whether there will be a positive effect. During the study blood sampling will take place. Bruising can occur. The amino acid mixtures have an unpleasant taste. Nausea can occur during and after drinking the mixtures.

Where is the study run from?
The study was set up by the Radboud University Nijmegen Medical Centre, Department of General Internal Medicine, Nijmegen Expert Centre Chronic Fatigue and Donders Institute for Brain, Cognition and Behaviour (Netherlands).

When is the study starting and how long is it expected to run for?
The study ran between June and December 2011.

Who is funding the study?
Funding was provided by Prof. dr. J.K. Buitelaar
Radboud University Nijmegen Medical Center Donders Institute for Brain, Cognition and Behavior
Dept of Cognitive Neuroscience
P.O. Box 9101 (204)
6500 HB Nijmegen

Who is the main contact?
Gerard The
gkh.the@gmail.com

Trial website

Contact information

Type

Scientific

Primary contact

Mr Gerard The

ORCID ID

Contact details

Glenn Millerlaan 10
Goes
4462LN
Netherlands
+31 11 842 52 45
gkh.the@gmail.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

The effect of acute tryptophan depletion in chronic fatigue syndrome, a pilot study.

Acronym

Study hypothesis

There is clinical and experimental evidence implicating enhanced serotonin metabolism in chronic fatigue syndrome. It is hypothesed that reducing central serotonin levels is effective in chronic fatigue syndrome.

Ethics approval

Radboud University Nijmegen Medical Centre, 01/09/2005, ref: 2005/167

Study design

Placebo-controlled cross-over study

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Pathophysiology of chronic fatigue syndrome

Intervention

Acute Tryptophan Depletion (ATD) is a reliable and reversible challenge test for serotonin.
It has widely used to investigate the role of serotonin in a variety of psychiatric disorders.
ATD is a method that significantly reduces central serotonin in human subjects. ATD is a technique that uses a combination of low tryptophan diet and a tryptophan-deficient protein load containing large amounts of other large neutral amino acids to produce maximal brain tryptophan and serotonin depletion. Within a few hours serotonin depletion can be achieved.
The effect of ATD on CFS-related symptoms, like fatigue, concentration and mood will be assessed.
Tryptophan and other amino acids levels will be assessed.
There are two test-days. On each test day baseline assessments (self-report questionnaires and blood sampling) will take place in the morning. Five hours after ingestion of the ATD mixture or the dummy mixture the assessments will be repeated. Each test day starts at 8.00 hrs and ends at 16:00 hrs.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measure

1. Fatigue severity
2. Concentration
3. Mood

Secondary outcome measures

No secondary outcome measures

Overall trial start date

01/06/2011

Overall trial end date

31/12/2011

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Female CFS-patients, according to CDC criteria
2. Aged 18 - 40 years
3. Written informed consent

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

5

Participant exclusion criteria

1. Nursing or pregnant women
2. Current psychiatric comorbidity
3. Vegetarians
4. Use of psychotropic drugs: current or previous month
5. Current or previous engagement in CFS research

Recruitment start date

01/06/2011

Recruitment end date

31/12/2011

Locations

Countries of recruitment

Netherlands

Trial participating centre

Glenn Millerlaan 10
Goes
4462LN
Netherlands

Sponsor information

Organisation

Radboud University Nijmegen Medical Center (Netherlands)

Sponsor details

P.O. Box 9101 (547)
Nijmegen
6500 HB
Netherlands
+31 24 361 11 11
gkh.the@gmail.com