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Trial registered on ANZCTR


Registration number
ACTRN12616001561471
Ethics application status
Approved
Date submitted
1/11/2016
Date registered
11/11/2016
Date last updated
13/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Treatment of Adolescents with Depression (TRACED): A pilot study on predictors for treatment response
Scientific title
Treatment of Adolescents with Depression (TRACED): A pilot study on Acute Tryptophan Depletion as a predictor for treatment response
Secondary ID [1] 290434 0
None
Universal Trial Number (UTN)
Trial acronym
TRACED
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Depression 300782 0
Condition category
Condition code
Mental Health 300612 300612 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention that will be applied in this trial is known as Acute Tryptophan Depletion (ATD). ATD is a dietary method that diminishes brain serotonin (5-HT) synthesis for a short period of 5 to 7 hours.

This study will consist of a randomised double-blind within subject repeated measures design of ATD or a balanced control condition (BAL) prior to pharmacological treatment as usual (TAS) with fluoxetine in adolescent patients with Major Depressive Disorder (MDD).
Prior to study participation, participants will be provided with an information sheet and consent form. Informed consent will be obtained from both the subjects and their parents/guardians.

This study will consist of two phases, Phase A and Phase B. Phase A will be conducted over two study days, spaced one week apart. On each study day, participants will either participate in the ATD or the BAL condition.

The ATD challenge procedure is as follows: The Moja-De ATD protocol employs amino acid administration within an aqueous suspension, in which the relevant amino acid quantities are linked to the participants’ body weights. The amino acid quantities ATD Moja-De are (dosage per 10 kg of body weight): L-phenylalanine (PHE 1.32 g), L-leucine (LEU 1.32 g), L-isoleucine (ILE 0.84 g), L-methionine (MET 0.5 g), L-valine (VAL 0.96 g), L-threonine (THR 0.6 g), and L-lysine (LYS 0.96 g). The BAL beverage contains the same amino acid quantities with an additional 0.7 g of L-tryptophan (TRP) per 10 kg of body weight. Research has shown that ATD is a safe and effective serotonergic challenge procedure, and that it can be safely used in minors (Moja-De ATD-test protocol). The amino acid mixtures will be prepared by an approved manufacturing facility. The ATD amino acid beverage is made up of the 7 dry amino acid as per the above calculations / 100 kg subject dissolved in 200mL with SyrSpend SF (Purified Water, Modified Food Starch, Sodium Citrate, Citric Acid, Malic Acid, Sodium Benzoate, Sucralose, Simethicone and Cherry Flavour). Each subject receives a proportional amount of ATD amino acids within an aqueous suspension according to the individual body weight. For example, a 50 kg subject will receive 100 mL SyrSpend SF with the respective amino acids related to the individual body weight.

The BAL beverage is made up of the same 7 dry amino acids in the ATD with the addition of tryptophan (a total of 8 amino acids) in the same way as the ATD beverage. Each subject receives a proportional amount of BAL amino acids within an aqueous suspension according to the individual body weight.

Following the administration of both ATD / BAL beverages, Apple juice will be offered following the mixture to wash out the taste.

Tryptophan free breakfast and lunch will be provided to participants on both study days.

After the intake of the challenge procedures (ATD or BAL), behavioural experiments will be conducted, including an attention testing battery, an emotional face recognition task, and a reversal-learning task.

The randomisation procedure will be managed by Princess Margaret Hospital Clinical Trials Pharmacy.

In Phase A 8 blood samples (3 mls each; 24 mls total) will be taken from each subject on each of the study days. 3 mls will be taken at baseline followed by 3mls every hour over 7 hours. An IV cannula will be placed by an experienced medical doctor which will remain in place so that regular blood samples can be obtained. The baseline blood sample will be taken after the IV cannula is inserted. The IV cannula will then be flushed with 3 – 4 mls of normal saline to maintain patency. For each subsequent blood sample that is taken, 2 – 3 mls of blood will be drawn and discarded before a definitive blood sample is collected. The IV cannula will then be flushed with 3-4 mls of normal saline.

Phase B will take place over a period of 12 weeks, where participants will be reviewed by a Consultant Psychiatrist once per week. During these 12 weeks, participants will be prescribed and administered a dose of fluoxetine of 20mg per day after an introduction period of 7 days with 10mg. The mode of administration of fluoxetine will be an oral tablet. This medication regime is in line with the NICE guidelines. Adherence to fluoxetine will be monitored through the return of an empty drug packet.

In Phase B, further blood samples for each subject will be taken on a weekly basis over the 12 week phase.

During Phase A and Phase B, participants’ mood will be monitored using the Beck Depression Inventory, the Hamilton Depression Rating Scale, and the Revised Children’s Depression Rating Scale.
Intervention code [1] 296276 0
Treatment: Drugs
Intervention code [2] 296277 0
Diagnosis / Prognosis
Comparator / control treatment
This study will consist of a randomised double-blind within subject repeated measures design. Individuals will undertake the ATD ("intervention") challenge procedure, and also the BAL procedure, which serves as the placebo condition.
Control group
Placebo

Outcomes
Primary outcome [1] 300038 0
Mood, assessed by Psychiatric Review
Timepoint [1] 300038 0
3.5 hours after ingestion of ATD/BAL challenge procedure
Primary outcome [2] 300052 0
Emotional face recognition, assessed by an emotional face recognition paradigm
Timepoint [2] 300052 0
3.5 hours after ATD / BAL ingestion
Primary outcome [3] 300056 0
Reversal learning paradigm; same paradigm as the one used in the study by Cools, Altamirano, Esposito (2006) (article titled: Reversal learning in Parkinson's disease depends
on medication status and outcome valence).
Timepoint [3] 300056 0
3.5 hours after ingestion of ATD/BAL challenge procedure
Secondary outcome [1] 328876 0
Mood will be assessed via a Mental State Examination
Timepoint [1] 328876 0
At the end of each study day in Phase A.
Secondary outcome [2] 329190 0
Amino acids concentration in blood, measured by blood samples
Timepoint [2] 329190 0
Every hour for eight hours, following ingestion of ATD / BAL beverage.

Eligibility
Key inclusion criteria
1. Confirmed diagnosis of MDD (ICD-10 or DSM-V).
2. No current suicidal ideation or suicidal plans
3. No other psychiatric co-medications at study entry.
4. IQ > 85
5. No active or past eating disorder
Minimum age
12 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Current abuse of alcohol and use of illicit substances
2. Pregnancy in female participants
3. Chronic medical or neurological disorder
4. Subjects whose primary language is not English
5. Treatment with other histaminergic or dopaminergic medications
6. Disorders of amino acid metabolism
7. Contraindications against the use of fluoxetine

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be concealed, and randomisation will be conducted by Princess Margaret Hospital Clinical Trials Pharmacy. Allocation will be concealed as pharmacy will provide a sealed opaque envelope with the coding for each mixture pair.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis
To examine changes in response to ATD (mood, cognitive parameters and tasks, amino acid concentrations, etc.) as well as after treatment (mood symptoms, cognition, SSRI monitoring) a series of repeated measures ANOVAs will be conducted with time (baseline, ATD administration and 12 weeks into treatment) and challenge procedure (ATD/BAL administration) as within-subject factors.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/12/2017
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 294848 0
Government body
Name [1] 294848 0
Telethon Perth Children's Hospital Research Fund
Country [1] 294848 0
Australia
Primary sponsor type
University
Name
The Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, The University of Western Australia
Address
35 Stirling Highway (M561)
Crawley, 6009
Western Australia
Australia
Country
Australia
Secondary sponsor category [1] 293688 0
None
Name [1] 293688 0
None
Address [1] 293688 0
Country [1] 293688 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296236 0
Princess Margaret Hospital Human Research Ethics Committee
Ethics committee address [1] 296236 0
Ethics committee country [1] 296236 0
Australia
Date submitted for ethics approval [1] 296236 0
Approval date [1] 296236 0
16/12/2015
Ethics approval number [1] 296236 0
2015203EP

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 70070 0
Prof Florian Zepf
Address 70070 0
The University of Western Australia
35 Stirling Highway M561
Crawley, 6009
Western Australia
Australia
Country 70070 0
Australia
Phone 70070 0
+6189340 8606
Fax 70070 0
Email 70070 0
florian.zepf@uwa.edu.au
Contact person for public queries
Name 70071 0
Janice Wong
Address 70071 0
Child and Adolescent Mental Health Services (CAMHS)
70 Hay Street
Subiaco, 6008
Western Australia
Australia
Country 70071 0
Australia
Phone 70071 0
+61863895835
Fax 70071 0
Email 70071 0
janice.wong@research.uwa.edu.au
Contact person for scientific queries
Name 70072 0
Richard Stewart
Address 70072 0
Bentley Health Service
35 Mills Street
Bentley, 6102
Western Australia
Country 70072 0
Australia
Phone 70072 0
+6189416 3800
Fax 70072 0
Email 70072 0
richard.stewart@health.wa.gov.au

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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIUsing acute tryptophan depletion to investigate predictors of treatment response in adolescents with major depressive disorder: study protocol for a randomised controlled trial2018https://doi.org/10.1186/s13063-018-2791-4
N.B. These documents automatically identified may not have been verified by the study sponsor.