Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12608000531314
Ethics application status
Approved
Date submitted
13/08/2008
Date registered
15/10/2008
Date last updated
4/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Serotonin and resilience to trauma-related exposure in serotonin reuptake inhibitor-recovered posttraumatic stress disorder
Scientific title
Tryptophan depletion paradigm increases the subjective and physiological responses to trauma-related stimuli in selective serotonin reuptake inhibitors-recovered patients with posttraumatic stress disorder
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Posttraumatic stress disorder 3548 0
Condition category
Condition code
Mental Health 3704 3704 0 0
Anxiety

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Acute tryptophan depletion through the ingestion of a amino acid mixture without triptophan (100g), which stimulates the liver to produce proteins and leads to competition to cross the blood-brain barrier. This mixture is administered only twice: in the morning of the test day and in the morning of the control day (both at 9.30 a.m.). The mixture was orally administered.
Its effects are rapidly reversed with reinstatement of the normal alimentation so the week between test and control procedures functions as wash-out period.
Intervention code [1] 3260 0
Other interventions
Comparator / control treatment
Amino acid mixture with L-alanine (5.5g); L-arginine (4.9g); L-cysteine HCl H2O (3.91g); Glycine (3.2g); L-histidine (3.2g); L-isoleucine (8.0g); L-leucine (13.5g); L-lysine HCL (11.0g); L-methionine (3.0g); L-phenylalanine (5.7g); L-proline (12.2g); L-serine (6.9g); L-threonine (6.5g); L-tyrosine (6.9g); L-valine (8.9g); [total: 100g].

The same mixture as applied in the intervention day [100g] plus L-tryptophan 2.3g function as placebo as it does not leads to depletion.

Both mixtures are administered per mouth in the morning of the test day (100g) and in the morning of the placebo day (100g + 2.3g of tryptophan). Both mixtures are administered only once a day at 9.30 a.m.
Control group
Placebo

Outcomes
Primary outcome [1] 4608 0
Visual analogue scales anchored to the following terms (in Portuguese): Suffering caused by traumatic memories, as tough the event was reoccurring , out of your body, emotionally numb, anger, difficulty concentrating, hypervigilance, startle, palpitations, guilt, helplessness, sadness, similar to what you used to feel before treatment
Timepoint [1] 4608 0
At baseline (9.00 a.m.) and after the administration of the drug at 11.00 a.m., 1.30 p.m., 2.50 p.m., 3.00 p.m., and 4.00
Secondary outcome [1] 7775 0
Speilberger state anxiety inventory
Timepoint [1] 7775 0
At baseline (9.00 a.m.) and after the administration of the drug at 11.00 a.m., 1.30 p.m., 2.50 p.m., 3.00 p.m., and 4.00
Secondary outcome [2] 7776 0
Davidson trauma scale (state version). In the state version we exclude the itens that measure "distressing dreams", "going into situations which reminds the event" and "trouble falling asleep". Patients only have to score the severity for what they are feeling "right now" and the total score is used to measure the symptoms.
Timepoint [2] 7776 0
At baseline (9.00 a.m.) and after the administration of the drug at 11.00 a.m., 1.30 p.m., 2.50 p.m., 3.00 p.m., and 4.00
Secondary outcome [3] 7777 0
"Profile of mood states" scale: Patients only have to score the severity for what they are feeling "right now" and the total score is used to measure the symptoms.
Timepoint [3] 7777 0
At baseline (9.00 a.m.) and after the administration of the drug at, 1.30 p.m., 3.00 p.m., and 4.00

Eligibility
Key inclusion criteria
Posttraumatic stress disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria; make good response to a selective serotonin reuptake inhibitors (cllinical dose ajusted)
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Comorbid bipolar disirder, psychotic disorder, substance misuse disorder, major madical condition and (or) the use of other psychiatric medication

Study design
Purpose of the study
Educational / counselling / training
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
There was no allocation to be concealed. Subjects were not allocated in different groups (crossover study).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by coin-tossing
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/02/2006
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment outside Australia
Country [1] 1150 0
Brazil
State/province [1] 1150 0
Sao Paulo

Funding & Sponsors
Funding source category [1] 3727 0
Government body
Name [1] 3727 0
Fundaco de Amparo a Pesquisa do Estado de Sao Paulo
Country [1] 3727 0
Brazil
Primary sponsor type
Government body
Name
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
Address
R. Pio XI, 1500 - Alto da Lapa - CEP 05468-901 - Sao Paulo/SP - Brasil
Country
Brazil
Secondary sponsor category [1] 3345 0
None
Name [1] 3345 0
Address [1] 3345 0
Country [1] 3345 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5781 0
Comissao de Etica para Analise de Projetos de Pesquisa (CAPPesq) do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
Ethics committee address [1] 5781 0
R. Dr. Ovideo Pires de Campos, 255, 5 andar - 05430-010 / Sao Paulo - Brasil
Ethics committee country [1] 5781 0
Brazil
Date submitted for ethics approval [1] 5781 0
Approval date [1] 5781 0
25/08/2005
Ethics approval number [1] 5781 0
538/05

Summary
Brief summary
Selective serotonin reuptake inhibitors are the first-line treatment for posttraumatic stress disorder but their mechanism of action is unclear. Though an effect on stress resilience is postulated Serotonin helps regulate stress responses in other anxiety disorders. The main objective of this study is to examine the role of serotonin in resilience to trauma-related exposure through tryptophan depletion paradigm. Our main hypothesis hypothesis is that exposure to trauma-related stimuli leads to greater subjective and physiological responses under acute tryptophan depletion than under control conditions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28836 0
Address 28836 0
Country 28836 0
Phone 28836 0
Fax 28836 0
Email 28836 0
Contact person for public queries
Name 11993 0
Felipe Corchs
Address 11993 0
R. Dr. Ovidio Pires de Campos, 785 - AMBAN-IPq-HC-FMUSP
Sao Paulo, Sao Paulo 05430-010
Brasil
Country 11993 0
Brazil
Phone 11993 0
+55 11 30696988
Fax 11993 0
+55 11 30696988
Email 11993 0
[email protected]
Contact person for scientific queries
Name 2921 0
Felipe Corchs
Address 2921 0
R. Dr. Ovidio Pires de Campos, 785 - AMBAN-IPq-HC-FMUSP
Sao Paulo, Sao Paulo 05430-010
Brasil
Country 2921 0
Brazil
Phone 2921 0
+55 11 30696988
Fax 2921 0
+55 11 30696988
Email 2921 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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