Minocycline Augmentation to Clozapine
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      The proposed pilot study will compare minocycline augmentation with clozapine in individuals
      with high vs low inflammation as measured by CRP. Investigators hypothesize that minocycline
      will be well tolerated and will result in an improvement in the symptoms of schizophrenia,
      cognition, as well as improve the quality of life for patients preferentially in patients
      with high CRPs. Investigators plan to use a variety of different scales to measure
      improvement in the varying symptoms of schizophrenia as well as cognitive function, which
      will be administered to patients at three week intervals for a total study time of twelve
      weeks. Investigators hypothesize that minocycline could prove to be an effective, well
      tolerated, and inexpensive medication for treatment resistant patients with schizophrenia
      whom have particular difficulties with social interactions, obtaining and maintaining
      employment, and overall quality of life. Furthermore, investigators hypothesize that the data
      obtained in this study will contribute to the ongoing exploration of the role of inflammation
      in the brain of patients with schizophrenia and help understand and target the role of
      various inflammatory markers in the pathophysiology and treatment of treatment resistant
      schizophrenia.
    

Detailed description: 
      Schizophrenia is a major mental illness characterized by a variety of different symptoms
      including hallucinations, paranoia, difficulties with formulating and expressing thoughts,
      feelings similar to depression, and problems with cognitive processes. Individuals with
      schizophrenia are usually treated with a class of medications called anti-psychotics, which
      typically help alleviate some of the symptoms of the disorder. In general, anti-psychotic
      medications do not completely cure the disorder, and many patients are left with some degree
      of ongoing symptoms. Furthermore, it is estimated that 20-30% of individuals with
      schizophrenia are considered treatment refractory or resistant and do not respond to
      anti-psychotic medications. The Food and Drug Administration has approved one antipsychotic
      medication for use in patients who are considered to have treatment resistant schizophrenia
      (TRS). This medication, clozapine, has been shown to be beneficial for patients with TRS,
      though as many as 40-70% of patients fail to respond or are partially responsive to treatment
      with clozapine. In an extensive search of the medical and psychiatric literature, the study
      team has been impressed by the potential of minocycline, a tetracycline antibiotic, as an
      adjunctive therapy in patients with schizophrenia based on its reported neuroprotective and
      anti-inflammatory effects. It is a fairly inexpensive drug, well tolerated, and two
      randomized clinical trials have demonstrated favorable results in early-phase schizophrenia.
      Only one case series with two patients has investigated minocycline in patients with
      schizophrenia on clozapine. Minocycline is also an interesting medication for augmentation
      with clozapine, as investigators are interested in previous findings of increased
      inflammation in the brains of patients with schizophrenia and the potential role of
      inflammation in treatment resistant schizophrenia. Though there are many markers of increased
      inflammation in the brain, for this current study, investigators are interested in a general
      marker of inflammation called C-Reactive Protein (CRP). The study team hypothesizes that some
      patients may have increased levels of inflammation in the brain, as measured by the CRP level
      (drawn from peripheral blood), and that those patients with increased levels of CRP may
      respond better to augmentation with minocycline. The proposed pilot study will compare
      minocycline augmentation with clozapine in individuals with high vs low inflammation as
      measured by CRP. Investigators hypothesize that minocycline will be well tolerated and will
      result in an improvement in the symptoms of schizophrenia, cognition, as well as improve the
      quality of life for patients preferentially in patients with high CRPs. Investigators plan to
      use a variety of different scales to measure improvement in the varying symptoms of
      schizophrenia as well as cognitive function, which will be administered to patients at three
      week intervals for a total study time of twelve weeks. Investigators hypothesize that
      minocycline could prove to be an effective, well tolerated, and inexpensive medication for
      treatment resistant patients with schizophrenia whom have particular difficulties with social
      interactions, obtaining and maintaining employment, and overall quality of life. Furthermore,
      investigators hypothesize that the data obtained in this study will contribute to the ongoing
      exploration of the role of inflammation in the brain of patients with schizophrenia and help
      understand and target the role of various inflammatory markers in the pathophysiology and
      treatment of treatment resistant schizophrenia.
    

Intervention name(s): Minocycline
Intervention type(s): Drug
Intervention MeSH terms: Minocycline
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Schizophrenia; Clozapine; Minocycline