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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by Bambino Gesù Hospital and Research Institute
Sponsor:
Collaborators:
National Alliance for Research on Schizophrenia and Depression
Orygen Youth Health Research Centre
Information provided by (Responsible Party):
Marco Armando, Bambino Gesù Hospital and Research Institute
ClinicalTrials.gov Identifier:
NCT02070211
First received: February 17, 2014
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
22q11 Deletion Syndrome
Dietary Supplement: omega-3 PUFAs
Other: Standard care
Dietary Supplement: placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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.

Resource links provided by NLM:


Further study details as provided by Bambino Gesù Hospital and Research Institute:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    These instruments are widely used clinical scales for psychotic patients and guarantee standardized assessment when used with interview guides and operationalized anchor points.

  • 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 ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 80
Study Start Date: June 2014
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Dietary Supplement: 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.
Other Names:
  • fish oil
  • poly unsaturated fatty acids
Other: 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.
Placebo Comparator: 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
Other: 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.
Dietary Supplement: placebo
4 capsules of 0.7g of paraffin oil (which is not absorbed by the gastrointestinal tract) per day.

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
  Eligibility

Ages Eligible for Study:   12 Years to 26 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02070211

Contacts
Contact: Marco Armando, MD, PhD +39 06 6859 2030 marco.armando@opbg.net
Contact: Stefano Vicari, MD, PhD +39 06 6859 2453 stefano.vicari@opbg.net

Locations
Holy See (Vatican City State)
Bambino Gesù Hospital and Research Institute Not yet recruiting
Vatican City, Vatican City State, Holy See (Vatican City State), 00165
Contact: Marco Armando, MD, PhD       marco.armando@opbg.net   
Contact: Stefano Vicari, MD, PhD       stefano.vicari@opbg.net   
Principal Investigator: Marco Armando, MD, PhD         
Sponsors and Collaborators
Bambino Gesù Hospital and Research Institute
National Alliance for Research on Schizophrenia and Depression
Orygen Youth Health Research Centre
Investigators
Principal Investigator: Marco Armando, MD, PhD Bambino Gesù Hospital and Research Institute
  More Information

No publications provided

Responsible Party: Marco Armando, MD, PhD, Bambino Gesù Hospital and Research Institute
ClinicalTrials.gov Identifier: NCT02070211     History of Changes
Other Study ID Numbers: APS 1, 21278
Study First Received: February 17, 2014
Last Updated: February 21, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by Bambino Gesù Hospital and Research Institute:
Psychotic Disorder
22q11 Deletion Syndrome
Fatty Acids, Omega-3

Additional relevant MeSH terms:
Parathyroid Diseases
22q11 Deletion Syndrome
Craniofacial Abnormalities
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Lymphatic Abnormalities
Lymphatic Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Hypoparathyroidism
Endocrine System Diseases

ClinicalTrials.gov processed this record on August 28, 2014