Pentoxifylline Augmentation in Schizophrenia
Paraules clau
Resum
Descripció
there is some evidence for the role of phosphodiesterase (PDE) signaling system in pathophysiology of schizophrenia making this system a potential target for therapeutic agents. PDEs are a family of enzymes that hydrolyse cyclic nucleotides and thus play a key role in regulating intracellular levels of the second messenger cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate. Pentoxifylline (PTX) is a methylated xanthine derivative and a PDE inhibitor that is FDA-approved for the treatment of patients with intermittent claudication on the basis of chronic occlusive arterial disease of the limbs. It is known to inhibit platelet aggregation, increase erythrocyte flexibility or deformability, and reduce blood viscosity. The rationale for its use in schizophrenia is that it competitively inhibits PDEs, resulting in increased cAMP levels, the activation of protein kinase A (PKA), the inhibition of IL and TNF-α synthesis, and reduced inflammation. Furthermore, there is growing evidence to support the inflammatory hypothesis of schizophrenia, the investigators will also explore whether cytokine levels mediate the response from pentoxifylline treatment.
Dates
| Darrera verificació: | 06/30/2020 |
| Primer enviat: | 09/14/2019 |
| Inscripció estimada enviada: | 09/15/2019 |
| Publicat per primera vegada: | 09/17/2019 |
| Última actualització enviada: | 07/06/2020 |
| Publicació de l'última actualització: | 07/07/2020 |
| Data d'inici de l'estudi real: | 12/31/2018 |
| Data estimada de finalització primària: | 12/29/2020 |
| Data estimada de finalització de l’estudi: | 12/30/2020 |
Condició o malaltia
Intervenció / tractament
Drug: Control group
Drug: Pentoxifylline group
Fase
Grups de braços
| Braç | Intervenció / tractament |
|---|---|
| Placebo Comparator: Control group Equivalent Placebo will be given | Drug: Control group Placebo tablets PLUS Risperidone 2 mg tablet up to 6 mg/day |
| Experimental: Pentoxifylline group Pentoxifylline will be given orally at 1200 mg a day for 4 months | Drug: Pentoxifylline group Pentoxifylline tablet PLUS Risperidone 2 mg tablet up to 6 mg/day |
Criteris d'elegibilitat
| Edats elegibles per estudiar | 18 Years Per a 18 Years |
| Sexes elegibles per estudiar | All |
| Accepta voluntaris saludables | Sí |
| Criteris | Inclusion Criteria: - Ages between 18-40 years - Males & females - Current DSM-IV diagnosis of schizophrenia or schizoaffective disorder confirmed by the Mini-International Neuropsychiatric Interview (M.I.N.I.) conducted by a trained psychiatrist. - Treatment with a stable dose of second generation antipsychotic medication for at least 1 months prior to study entry 200-600 mg/day chlorpromazine equivalent doses); - Evidence of stable symptomatology for 12 weeks as evidenced by no hospitalizations for schizophrenia, no increase in level of psychiatric care due to worsening of symptoms, no ER use for symptoms of schizophrenia and no significant changes to antipsychotic medication or dose (>25%) in the past 12 weeks. - Baseline total score between 40 and 65 on the Brief Psychiatric Rating Scale (BPRS); Raw score of 12 or higher on the Wechsler Test of Adult Reading (WTAR) (estimates premorbid IQ). - Able to comprehend the procedure and aims of the study to provide informed consent Exclusion Criteria: - Acute, unstable, significant or untreated medical illness beside schizophrenia; - Pregnant or breast-feeding females; - History of substance abuse or dependence in the past 3 months. - Known contraindication to pentoxifylline treatment. - Any serious or life‐threatening medical conditions or neurological problem, severe extrapyramidal symptoms, history of abnormal bleeding, presence of hypothyroidism, renal disease, cardiovascular problems, rising liver transaminases to 3 times the upper limit of normal or higher |
Resultat
Mesures de resultats primaris
1. Treatment-induced change in total score on Positive and Negative Syndrome Scale (PANSS) [Baseline to week 16 of the study]
Mesures de resultats secundaris
1. Treatment-induced change in MATRICS Cognitive Consensus Battery (MCCB) [Baseline and week 16 of the study]
2. Treatment-induced changes in plasma level of cytokines [Baseline and week 16 of the study]
