title: Adjuvant therapy with minocycline for schizophrenia (The MINOS Trial): study protocol for a double-blind randomized placebo-controlled trial.
abstract: BACKGROUND
  Schizophrenia is understood to be a heterogeneous brain condition with overlapping symptom dimensions. The negative symptom dimension, with its protean cognitive manifestations, responds poorly to treatment, which can be a particular challenge in countries where clozapine therapy is not available. Preliminary data indicate that minocycline may be beneficial adjunct in the treatment of schizophrenia: positive, negative, and cognitive symptoms.In this study we aim to assess the efficacy of adjunctive minocycline to alleviate symptoms of schizophrenia in patients who have failed to respond to a therapeutic trial of antipsychotic medications.
  
  
  METHODS
  The study is a parallel group, double-blind, randomized, placebo-controlled trial. Participants will be adults (aged 18 years and above) with first episode or relapse episode of schizophrenia of under 5 years' duration. Patients who failed to show adequate therapeutic response to at least one antipsychotic medication given for a minimum of 4 weeks will be recruited from a psychiatry hospital in Addis Ababa and a psychiatry clinic in Butajira, Ethiopia. A total of 150 participants (75 in each arm) will be required to detect a five-point mean difference between the intervention arms adjusting for baseline symptom severity, at 90% power and 95% confidence. Patients in the intervention arm will receive minocycline (200 mg/day orally) added on to the regular antipsychotic medications participants are already on. Those in the placebo arm will receive an inactive compound identical in physical appearance to minocycline. Intervention will be offered for 12 weeks. Diagnosis will be established using the operational criteria for research (OPCRIT). Primary outcome measure will be a change in symptom severity measured using the positive and the negative syndrome scale for schizophrenia (PANSS). Secondary outcome measures will include changes in severity of negative symptoms, proportion achieving remission, and level of functioning. Whether changes are maintained post intervention will also be measured (PANSS). Key assessment for the primary outcome will be conducted at the end of trial (week 12). One post-intervention assessment will be conducted 4 weeks after the end of intervention (week 16) to determine sustainability of change.
  
  
  BACKGROUND
  Clinicaltrials.gov identifier: NCT01809158.
authors.affiliation: Department of psychiatry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia. abe.wassie@kcl.ac.uk.
authors.forename: Abebaw
authors.initials: A
authors.lastname: Fekadu
authors.forename: Miraf
authors.initials: M
authors.lastname: Mesfin
authors.forename: Girmay
authors.initials: G
authors.lastname: Medhin
authors.forename: Atalay
authors.initials: A
authors.lastname: Alem
authors.forename: Solomon
authors.initials: S
authors.lastname: Teferra
authors.forename: Tsehaysina
authors.initials: T
authors.lastname: Gebre-Eyesus
authors.forename: Teshale
authors.initials: T
authors.lastname: Seboxa
authors.forename: Abraham
authors.initials: A
authors.lastname: Assefa
authors.forename: Jemal
authors.initials: J
authors.lastname: Hussein
authors.forename: Martha T
authors.initials: MT
authors.lastname: Lemma
authors.forename: Christina
authors.initials: C
authors.lastname: Borba
authors.forename: David C
authors.initials: DC
authors.lastname: Henderson
authors.forename: Charlotte
authors.initials: C
authors.lastname: Hanlon
authors.forename: Teshome
authors.initials: T
authors.lastname: Shibre
mesh_terms: D000293:Adolescent; D000328:Adult; D002985:Clinical Protocols; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D008911:Minocycline / Q000627:therapeutic use*; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D018401:Sample Size; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D008911:Minocycline