Indicated Prevention With Long-chain Polyunsaturated Omega-3 Fatty Acids in Patients With 22q11 Microdeletion Syndrome.

NCT ID: NCT02070211

Last Updated: 2014-02-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2016-06-30

Brief 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.

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:

1. 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.

2. 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

omega-3 PUFAs in add on to standard care

omega-3 PUFA supplementation as an adjunct to non-neuroleptic, standard therapy in individuals with 22q11DS and UHR criteria for psychosis

Group Type: EXPERIMENTAL

omega-3 PUFAs

Intervention Type: DIETARY_SUPPLEMENT

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 care

Intervention Type: OTHER

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.

Placebo in add on to standard care

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

Group Type: PLACEBO_COMPARATOR

Standard care

Intervention Type: OTHER

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.

placebo

Intervention Type: DIETARY_SUPPLEMENT

4 capsules of 0.7g of paraffin oil (which is not absorbed by the gastrointestinal tract) per day.

Interventions

omega-3 PUFAs

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.

Intervention Type: DIETARY_SUPPLEMENT

Standard care

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.

Intervention Type: OTHER

placebo

4 capsules of 0.7g of paraffin oil (which is not absorbed by the gastrointestinal tract) per day.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

fish oil; poly unsaturated fatty acids

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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);
• 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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 26 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Alliance for Research on Schizophrenia and Depression

OTHER

Sponsor Role: collaborator

Orygen

OTHER

Sponsor Role: collaborator

Bambino Gesù Hospital and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Marco Armando

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marco Armando, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Bambino Gesù Hospital and Research Institute

Locations

Bambino Gesù Hospital and Research Institute

Vatican City, Vatican City State, Holy See

Countries

Holy See

Central Contacts

Marco Armando, MD, PhD

Role: CONTACT

marco.armando@opbg.net

+39 06 6859 2030

Stefano Vicari, MD, PhD

Role: CONTACT

stefano.vicari@opbg.net

+39 06 6859 2453

Facility Contacts

Marco Armando, MD, PhD

Role: primary

marco.armando@opbg.net

Stefano Vicari, MD, PhD

Role: backup

stefano.vicari@opbg.net

Other Identifiers

21278

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

APS 1

Identifier Type: -

Identifier Source: org_study_id