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

Bambino Gesù Hospital and Research Institute

Status and phase: Unknown; Phase 3; Phase 2

Conditions: 22q11 Deletion Syndrome

Treatments: Dietary Supplement: omega-3 PUFAs; Other: Standard care; Dietary Supplement: placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02070211

21278 (Other Grant/Funding Number)

APS 1

Details and patient eligibility

About

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.

Full 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

Enrollment: 80 estimated patients

Sex: All

Ages: 12 to 26 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups, including a placebo group

omega-3 PUFAs in add on to standard care

Experimental group

Description:

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

Treatment:

Dietary Supplement: omega-3 PUFAs

Other: Standard care

Placebo in add on to standard care

Placebo Comparator group

Description:

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

Treatment:

Dietary Supplement: placebo

Other: Standard care