22q11 Deletion SyndromePhase 2/3NCT02070211
Indicated Prevention With Long-chain Polyunsaturated Omega-3 Fatty Acids in Patients With 22q11 Microdeletion Syndrome.
A Phase 2/3 study testing omega-3 PUFAs in people with 22q11 Deletion Syndrome, run by Bambino Gesù Hospital and Research Institute at 1 site in Holy See.
Trial summary
The purpose of the present trial is to investigate the effects of omega-3 PUFAs in individuals aged 12-26 years with 22q11DS at ultra-high risk for developing a first episode of psychosis. Read more about this study
- Who is it for?
- Ages 12 to 26 years
- Conditions the study is for
- 22q11 Deletion Syndrome
- What is being tested?
- omega-3 PUFAs
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteHoly See
- Study dates
- Jun 2014to Jun 2016
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 26 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- written informed consent (for individuals under 18 written informed consent of parents is required);
- age between 12 and 26 years;
- UHR as classified by the CAARMS (Yung et al., 2005);
- genetic diagnosis of 22q11DS
Who cannot join
- acute suicidal behaviour (score of 6 on CAARMS item 7.3) or aggressive behaviour (score of 6 on CAARMS item 5.4);
- Drug abuse that contributed decisively to the presentation of the index episode, (dependency on morphine, cocaine, amphetamine, but not THC);
- Alcohol abuse if considered as major problem;
- Epilepsy; 5./IQ<70);
- Pregnancy and lactation;
- Previous history of antipsychotic drug treatment (> one week treatment);
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- Laboratory values more than 15% outside the normal range for transaminases, CRP or bleeding parameters;
- Individuals with organic brain syndrome;
- Individuals who are taking anticoagulants;
- Individuals who are taking omega-3 supplements, currently or within 8 weeks of being included in the trial;
- Individuals who have other, severe, intercurrent illness which in the opinion of the investigator may put them at risk or influence the results of the trial.
Trial locations and contacts
1 site in 1 country.
Holy See1 site
Bambino Gesù Hospital and Research Institute
Vatican City, Vatican City State, 00165
Marco Armando, MD, PhD, marco.armando@opbg.net
Stefano Vicari, MD, PhD, stefano.vicari@opbg.net
About this study
Official title: Indicated Prevention With Long-chain Polyunsaturated Omega-3 Fatty Acids in Patients With 22q11 Microdeletion Syndrome Genetically at High Risk for Psychosis: A Randomised, Double Blind, Placebo-controlled Treatment Trial.
The purpose of the present trial is to investigate the effects of omega-3 PUFAs in individuals aged 12-26 years with 22q11DS at ultra-high risk for developing a first episode of psychosis.
Read the detailed description
We will use a prospective, randomized, double-blind, placebo-controlled, single-centre study design. Eighty individuals aged 12-26 will be randomly assigned in two treatment conditions (40 in each arm) at the Department of Neuroscience, Children Hospital Bambino Gesù, Rome, Italy. Randomisation will be arranged by the Clinical Trials Department of the same hospital. Participants will receive 4 capsules (2 in the morning; 2 in the evening) for a period of 12 weeks. The active treatment is a supplement of yellow gelatine 0.625 g capsules containing concentrated marine fish oil. The daily dose of 4 capsules will provide approximately 700 mg of eicosapentaenoic acid (EPA, 20:5n3), 480 mg of docosahexaenoic acid (DHA, 22:6n3), and 7.6 mg of Vitamin E. Vitamin E is added as an antioxidant to fish oil capsules to stabilize highly unsaturated fatty acids. Participants will receive either 4 capsules of 0.7g marine fish oil or 4 capsules of 0.7g of paraffin oil (which is not absorbed by the gastrointestinal tract) per day. The daily dose of omega-3 PUFAs is based on our previous trail (Amminger et al., 2010).
All patients will receive standard treatment, which includes management by a psychiatrist or resident psychiatrist and non-neuroleptic pharmacotherapy as clinically indicated. Specifically, Cognitive-behavioural therapy (CBT) embedded within case management will be administered. The CBT will be based on the models developed at the PACE Clinic in Melbourne, in the EDIE trial, and in Cologne, as these have proven to be effective in RCTs. The number of sessions delivered will be captured for each client. In addition, fidelity will be monitored by therapists rating their own sessions on an established checklist of therapeutic interventions. Any additional psychosocial interventions delivered will also be documented. The case management component will consist of therapists addressing current interpersonal and social issues and providing practical help. 6 - 20 CBCM sessions will be provided within the first 6 months.
Hypotheses:
- Omega-3 PUFAs have a positive effect on clinical course and outcome in UHR+22q11DS individuals Specifically that at 12 months follow-up:
- The transition to psychosis rate is significantly lower in the omega-3 PUFA group
- Ratings on CAARMS, PANSS, MADRS, GAF improve significantly more in the omega-3 PUFA group
- Neuropsychological functioning is significantly better in the omega-3 PUFA group.
- Lipid metabolism characteristics described in schizophrenia will be more prevalent in individuals who make transition to psychosis
- Reduced omega-3 PUFAs and reduced nervonic acid (Amminger et al., 2011) and increased PLA2 activity at baseline characterize individuals who develop psychosis
- PLA2 activity will significantly decrease pre/post treatment in the omega-3 PUFA group
- Conditions
- 22q11 Deletion Syndrome
- Being tested
- omega-3 PUFAs, Standard care, placebo
- Keywords
- Psychotic Disorder, 22q11 Deletion Syndrome, Fatty Acids, Omega-3
- Medical subject headings
- 22q11 Deletion Syndrome, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
omega-3 PUFAsDietary supplement
Also called fish oil, poly unsaturated fatty acids
4 capsules (2 in the morning; 2 in the evening) for a period of 12 weeks. The active treatment is a supplement of yellow gelatine 0.625 g capsules containing concentrated marine fish oil. The daily dose of 4 capsules will provide approximately 700 mg of eicosapentaenoic acid (EPA, 20:5n3), 480 mg of docosahexaenoic acid (DHA, 22:6n3), and 7.6 mg of Vitamin E.
Standard careOther
Standard care includes management by a psychiatrist or resident psychiatrist and non-neuroleptic pharmacotherapy as clinically indicated. Specifically, Cognitive-behavioural therapy (CBT) embedded within case management will be administered. The CBT will be based on the models developed at the PACE Clinic in Melbourne, in the EDIE trial, and in Cologne, as these have proven to be effective in RCTs. The number of sessions delivered will be captured for each client. In addition, fidelity will be monitored by therapists rating their own sessions on an established checklist of therapeutic interventions.
placeboDietary supplement
4 capsules of 0.7g of paraffin oil (which is not absorbed by the gastrointestinal tract) per day.
| Study group | Role | What they receive |
|---|---|---|
| omega-3 PUFAs in add on to standard care | Experimental | omega-3 PUFA supplementation as an adjunct to non-neuroleptic, standard therapy in individuals with 22q11DS and UHR criteria for psychosis Receives: Dietary Supplement: omega-3 PUFAs; Other: Standard care |
| Placebo in add on to standard care | Placebo comparator | Placebo made by paraffin oil (not absorbed by the gastrointestinal tract) as an adjunct to non-neuroleptic, standard therapy in individuals with 22q11DS and UHR criteria for psychosis Receives: Other: Standard care; Dietary Supplement: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome measure for this study is the transition to psychosis rate measured by the Comprehensive Assessment of At Risk Mental States (CAARMS) (Yung et al., 2005),
Transition to psychosis is operationally defined, based on the CAARMS (Yung et al., 2005) criteria: 1./Abnormal thoughts held with delusional intensity occurring every day for one week or longer; 2./True hallucinations in any modality occurring every day for one week or longer; or 3./Formal thought disorder to the degree of incoherence and/or loose associations occurring every day for one week or longer
Measured: The time frame for the first outcome measure will be over the 12-month follow-up period.
Secondary outcomes (4)
The secondary outcome measures are the transition to psychosis rate measured by the CAARMS, the Positive and Negative Syndrome Scale (PANSS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Global Assessment of Functioning Scale (GAF)
These instruments are widely used clinical scales for psychotic patients and guarantee standardized assessment when used with interview guides and operationalized anchor points.
Measured: These scales will be performed at baseline, 4, 8, 12, 26, and 52 weeks.
Side effects of therapeutic interventions will be assessed using the UKU side effect rating scale (Lingjaerde et al., 1987).
Measured: Side effects will be assessed at baseline, 4, 8, 12, 26, and 52 weeks
Wechsler Adult Intelligence Scales-Revised, the Wechsler Memory Scale-Revised, the Wisconsin Card Sorting Test, Trail Making Test-Part A and B, the Continuous Performance Test, and the Finger Tapping Test: right and left
In accordance with Bilder et al. (2000) assessments will cover following neuropsychological functions: (1) memory (spatial short term memory, spatial working memory, visuospatial paired associate learning, pattern recognition, spatial recognition, delayed matching to sample), (2) executive, (3) attention, (4) language, (5) motor, (6) visuospatial.
Measured: The neuropsychological battery will be performed at baseline and after 12 weeks (pre/post study design) and at 12 months follow-up.
Blood samples: EDTA blood in standard glass tubes (no plastic tubes because of artifacts for omega-3 PUFA analysis)
Blood samples will be collected and centrifuged as soon as possible at 1500g for 15 minutes. inPLA2 sample: 1 tube (5ml) EDTA blood: Plasma, buffy coat and the top 2 mm of RBCs will be aspirated and frozen. Omega-3 PUFA sample: 1 tube (10ml) EDTA blood: second wash step required. Samples will be frozen at -80 degrees Celsius.
Measured: At baseline and after twelve weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2014 (estimated)
- Study startJun 2014
- Primary completionJun 2016 (estimated)
- Study completionJun 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 22q11 Deletion SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bambino Gesù Hospital and Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression, Orygen
- Responsible party
- Principal investigator, Marco Armando, Bambino Gesù Hospital and Research Institute
- Investigators
- Marco Armando, MD, PhD, Principal investigator, Bambino Gesù Hospital and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02070211
- Sponsor's protocol ID
- APS 1
- Other IDs
- 21278
- Status last verified
- Feb 2014
- First submitted
- 17 Feb 2014
- Last updated
- 25 Feb 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Indicated Prevention With Long-chain Polyunsaturated Omega-3 Fatty Acids in Patients With 22q11 Microdeletion Syndrome Genetically at High Risk for Psychosis: A Randomised, Double Blind, Placebo-controlled Treatment Trial.
- ClinicalTrials.gov ID
- NCT02070211
- Acronym / sponsor ID
- APS 1
- Conditions
- 22q11 Deletion Syndrome
- Keywords
- Psychotic Disorder, 22q11 Deletion Syndrome, Fatty Acids, Omega-3
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Bambino Gesù Hospital and Research InstituteUniversity, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression, Orygen
- Study start
- Jun 2014
- Primary completion
- Jun 2016 (estimated)
- Study completion
- Jun 2016 (estimated)
- First posted
- 25 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the present trial is to investigate the effects of omega-3 PUFAs in individuals aged 12-26 years with 22q11DS at ultra-high risk for developing a first episode of psychosis.
Detailed description
We will use a prospective, randomized, double-blind, placebo-controlled, single-centre study design. Eighty individuals aged 12-26 will be randomly assigned in two treatment conditions (40 in each arm) at the Department of Neuroscience, Children Hospital Bambino Gesù, Rome, Italy. Randomisation will be arranged by the Clinical Trials Department of the same hospital. Participants will receive 4 capsules (2 in the morning; 2 in the evening) for a period of 12 weeks. The active treatment is a supplement of yellow gelatine 0.625 g capsules containing concentrated marine fish oil. The daily dose of 4 capsules will provide approximately 700 mg of eicosapentaenoic acid (EPA, 20:5n3), 480 mg of docosahexaenoic acid (DHA, 22:6n3), and 7.6 mg of Vitamin E. Vitamin E is added as an antioxidant to fish oil capsules to stabilize highly unsaturated fatty acids. Participants will receive either 4 capsules of 0.7g marine fish oil or 4 capsules of 0.7g of paraffin oil (which is not absorbed by the gastrointestinal tract) per day. The daily dose of omega-3 PUFAs is based on our previous trail (Amminger et al., 2010).
All patients will receive standard treatment, which includes management by a psychiatrist or resident psychiatrist and non-neuroleptic pharmacotherapy as clinically indicated. Specifically, Cognitive-behavioural therapy (CBT) embedded within case management will be administered. The CBT will be based on the models developed at the PACE Clinic in Melbourne, in the EDIE trial, and in Cologne, as these have proven to be effective in RCTs. The number of sessions delivered will be captured for each client. In addition, fidelity will be monitored by therapists rating their own sessions on an established checklist of therapeutic interventions. Any additional psychosocial interventions delivered will also be documented. The case management component will consist of therapists addressing current interpersonal and social issues and providing practical help. 6 - 20 CBCM sessions will be provided within the first 6 months.
Hypotheses:
- Omega-3 PUFAs have a positive effect on clinical course and outcome in UHR+22q11DS individuals Specifically that at 12 months follow-up:
- The transition to psychosis rate is significantly lower in the omega-3 PUFA group
- Ratings on CAARMS, PANSS, MADRS, GAF improve significantly more in the omega-3 PUFA group
- Neuropsychological functioning is significantly better in the omega-3 PUFA group.
- Lipid metabolism characteristics described in schizophrenia will be more prevalent in individuals who make transition to psychosis
- Reduced omega-3 PUFAs and reduced nervonic acid (Amminger et al., 2011) and increased PLA2 activity at baseline characterize individuals who develop psychosis
- PLA2 activity will significantly decrease pre/post treatment in the omega-3 PUFA group
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| omega-3 PUFAs in add on to standard care | Experimental | Dietary Supplement: omega-3 PUFAs, Other: Standard careomega-3 PUFA supplementation as an adjunct to non-neuroleptic, standard therapy in individuals with 22q11DS and UHR criteria for psychosis |
| Placebo in add on to standard care | Placebo comparator | Other: Standard care, Dietary Supplement: placeboPlacebo made by paraffin oil (not absorbed by the gastrointestinal tract) as an adjunct to non-neuroleptic, standard therapy in individuals with 22q11DS and UHR criteria for psychosis |
Who may qualify
- Ages
- 12 to 26 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- written informed consent (for individuals under 18 written informed consent of parents is required);
- age between 12 and 26 years;
- UHR as classified by the CAARMS (Yung et al., 2005);
- genetic diagnosis of 22q11DS
Key exclusion criteria (11 listed)
- acute suicidal behaviour (score of 6 on CAARMS item 7.3) or aggressive behaviour (score of 6 on CAARMS item 5.4);
- Drug abuse that contributed decisively to the presentation of the index episode, (dependency on morphine, cocaine, amphetamine, but not THC);
- Alcohol abuse if considered as major problem;
- Epilepsy; 5./IQ<70);
- Pregnancy and lactation;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| omega-3 PUFAsAlso: fish oil, poly unsaturated fatty acids4 capsules (2 in the morning; 2 in the evening) for a period of 12 weeks. The active treatment is a supplement of yellow gelatine 0.625 g capsules containing concentrated marine fish oil. The daily dose of 4 capsules will provide approximately 700 mg of eicosapentaenoic acid (EPA, 20:5n3), 480 mg of docosahexaenoic acid (DHA, 22:6n3), and 7.6 mg of Vitamin E. | Dietary supplement | omega-3 PUFAs in add on to standard care |
| Standard careStandard care includes management by a psychiatrist or resident psychiatrist and non-neuroleptic pharmacotherapy as clinically indicated. Specifically, Cognitive-behavioural therapy (CBT) embedded within case management will be administered. The CBT will be based on the models developed at the PACE Clinic in Melbourne, in the EDIE trial, and in Cologne, as these have proven to be effective in RCTs. The number of sessions delivered will be captured for each client. In addition, fidelity will be monitored by therapists rating their own sessions on an established checklist of therapeutic interventions. | Other | Placebo in add on to standard care, omega-3 PUFAs in add on to standard care |
| placebo4 capsules of 0.7g of paraffin oil (which is not absorbed by the gastrointestinal tract) per day. | Dietary supplement | Placebo in add on to standard care |
Primary outcome
The primary outcome measure for this study is the transition to psychosis rate measured by the Comprehensive Assessment of At Risk Mental States (CAARMS) (Yung et al., 2005),
Time frame: The time frame for the first outcome measure will be over the 12-month follow-up period.
Transition to psychosis is operationally defined, based on the CAARMS (Yung et al., 2005) criteria: 1./Abnormal thoughts held with delusional intensity occurring every day for one week or longer; 2./True hallucinations in any modality occurring every day for one week or longer; or 3./Formal thought disorder to the degree of incoherence and/or loose associations occurring every day for one week or longer
4 secondary outcomes
The secondary outcome measures are the transition to psychosis rate measured by the CAARMS, the Positive and Negative Syndrome Scale (PANSS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Global Assessment of Functioning Scale (GAF)
Time frame: These scales will be performed at baseline, 4, 8, 12, 26, and 52 weeks.
Side effects of therapeutic interventions will be assessed using the UKU side effect rating scale (Lingjaerde et al., 1987).
Time frame: Side effects will be assessed at baseline, 4, 8, 12, 26, and 52 weeks
Wechsler Adult Intelligence Scales-Revised, the Wechsler Memory Scale-Revised, the Wisconsin Card Sorting Test, Trail Making Test-Part A and B, the Continuous Performance Test, and the Finger Tapping Test: right and left
Time frame: The neuropsychological battery will be performed at baseline and after 12 weeks (pre/post study design) and at 12 months follow-up.
Blood samples: EDTA blood in standard glass tubes (no plastic tubes because of artifacts for omega-3 PUFA analysis)
Time frame: At baseline and after twelve weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marco Armando, MD, PhD principal investigator
Bambino Gesù Hospital and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing omega-3 PUFAs in people with 22q11 Deletion Syndrome, run by Bambino Gesù Hospital and Research Institute at 1 site in Holy See.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Holy See. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marco Armando, MD, PhD (+39 06 6859 2030, marco.armando@opbg.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome measure for this study is the transition to psychosis rate measured by the Comprehensive Assessment of At Risk Mental States (CAARMS) (Yung et al., 2005), (time frame: The time frame for the first outcome measure will be over the 12-month follow-up period.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2014.