Minocycline and/or Omega-3 Fatty Acids Added to Treatment as Usual for At Risk Mental States (NAYAB)

A Randomised Double Blind Placebo Controlled Pilot Study of Minocycline and/or Omega-3 Fatty Acids Added to Treatment as Usual for At Risk Mental States

This is a randomized double-blind placebo controlled trial which aims to evaluate the efficacy and tolerability of minocycline and Omega-3 fatty acids for patients with ARMS. Specifically to determine whether the addition of minocycline and / or Omega-3 fatty acids to Treatment as Usual in an operationalized ARMS population in Pakistan:

Study Overview

• Status: Completed
• Conditions: Psychosis; At Risk Mental State (ARMS)
• Intervention / Treatment: Drug: Placebo; Drug: Minocycline; Drug: Omega-3 fatty acids; Drug: Minocycline Plus Omega-3 fatty acids

Detailed Description

Primary hypothesis is that the persons with ARMS who are prescribed minocycline and / or Omega-3 fatty acids will have reduced transition rates to psychosis over a one year follow up period (from baseline) compared with Treatment-As-Usual (TAU). The transition rates will be lowest in the group receiving minocycline and Omega-3 fatty acids in combination.

Secondary objective is to determine that the Persons with ARMS who are prescribed minocycline and / or Omega-3fatty acids in combination will have greatest symptom reduction compared with TAU.

This study will be a six-month intervention of minocycline and/or Omega-3 fatty acids added to TAU in patients with ARMS, using a randomised, placebo-controlled, double-blind factorial design.The study will be a four-arm trial: one arm will receive minocycline with TAU; the second arm will receive Omega-3 fatty acids with TAU; the third arm will receive both minocycline and Omega-3 fatty acids with TAU; the fourth arm will receive placebo with TAU.

• Study Type: Interventional
• Enrollment (Actual): 326
• Phase: Phase 2

Contacts and Locations

Study Locations

• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan, 72000
      • Abasi Shaheed Hospital
    • Karachi, Sindh, Pakistan, 72000
      • Civil Hospital Karachi
    • Karachi, Sindh, Pakistan, 72000
      • Karwn e Hayat
    • Karachi, Sindh, Pakistan
      • Colleges and Universities
    • Karachi, Sindh, Pakistan
      • Community
    • Karachi, Sindh, Pakistan
      • General Practitioners (GPs)
    • Karachi, Sindh, Pakistan
      • Institute of Behavioral Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 35 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female help seeking individuals aged between 16-35 years.
2. Meets at least one of the criteria for ARMS (see CAARMS Operationalized Intake Criteria section below).
3. Assessed as competent to provide informed consent.

Exclusion Criteria:

1. History ofpreviously experiencing a psychotic illness (treated or untreated).
2. IQ < 70 and/or history of learning disability.
3. Any pre-existing inflammatory conditions e.g. rheumatoid arthritis.
4. Organic brain disease e.g. epilepsy.
5. treatment with an antipsychotic or mood-stabilising agent.
6. Prior history of intolerance or serious side effects (hepatotoxicity, photosensitivity, blood dyscrasias) to any of the tetracyclines or Omega-3 fatty acids.
7. Concomitant penicillin therapy or concomitant anticoagulant therapy.
8. Active substance abuse (except nicotine or caffeine) or dependence within the last three months, according to DSM-V criteria.
9. Treatment with warfarin or lamotrigine.
10. Current or previous treatment with tetracycline antibiotics or Omega-3 fatty acids in the preceding three months before study entry.
11. Current treatment with any anti-inflammatory medication.
12. Treatment with electroconvulsive therapy within the 12 weeks preceding the study.
13. Active expression of suicidal ideation (CAARMS item 7.3 severity score 6) or current aggression/dangerous behaviour (CAARMS item 5.4 severity score 6). 14. Relevant current or past hematologic, hepatic, renal, neurological or other medical disorder that in the opinion of the principal investigator may interfere with the study.

15. Pregnant or breastfeeding females.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Minocycline; Minocycline added to TAU Minocycline will be administered in 200mg once daily dose	Drug: Minocycline; Minocycline added to TAU Minocycline will be administered in 200mg once daily dose
ACTIVE_COMPARATOR: Omega-3 fatty acids; Omega-3 fatty acids added to TAU Omega-3 fatty acids will be administered in 1.2mg once daily dose	Drug: Omega-3 fatty acids; Omega-3 fatty acids added to TAU Omega-3 fatty acids will be administered in 1.2g once daily dose
ACTIVE_COMPARATOR: Placebo; Placebo added to TAU	Drug: Placebo; Placebo added to TAU
ACTIVE_COMPARATOR: Minocycline Plus Omega-3 fatty acids; Minocycline+Omega-3 fatty acids added to TAU ,Minocyline will be administered in 200mg once daily dose and Omega-3 fatty acids 1.2 g taken as once daily dose	Drug: Minocycline Plus Omega-3 fatty acids; Minocycline will be administered in 200mg once daily dose and Omega-3 fatty acid 1.2g taken as once daily dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transition to psychotic disorder	Structure Clinical interview for DSM-IV(SCID) (Michael B et al,. 2002) to confirm the transition to psychosis.	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measured severity ofAt Risk of Mental State ( ARMS) symptoms	Comprehensive Assessment of At-Risk Mental States (CAARMS) (Berger, GEet al2006).A semi-structured interview that assists in the identification of individuals at risk of developing a first-episode psychotic disorder and measured the severity of ARMS symptoms.	12 Months

Collaborators and Investigators

• Sponsor: Pakistan Institute of Living and Learning

Publications and helpful links

General Publications

• Qurashi I, Chaudhry IB, Khoso AB, Farooque S, Lane S, Husain MO, Chu S, Sarginson J, Hamarani M, Naqvi HA, Razzaque B, Minhas FA, Yung AR, Deakin JFW, Husain N. A randomised, double-blind, placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at-risk mental states (NAYAB): study protocol. Trials. 2017 Nov 9;18(1):524. doi: 10.1186/s13063-017-2275-y.

Helpful Links

• Website of Pakistan Institute of Learning and Living

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (ACTUAL): December 1, 2018
• Study Completion (ACTUAL): March 1, 2019

Study Registration Dates

• First Submitted: October 3, 2015
• First Submitted That Met QC Criteria: October 3, 2015
• First Posted (ESTIMATE): October 6, 2015

Study Record Updates

• Last Update Posted (ACTUAL): August 5, 2019
• Last Update Submitted That Met QC Criteria: August 2, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Psychosis; At Risk of Mental State; Prodromal Phase
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders; Mental Disorders; Anti-Infective Agents; Anti-Bacterial Agents; Minocycline
• Other Study ID Numbers: PILL-NAYAB-001