Ignite Creation Date:
2024-05-06 @ 12:31 PM
Last Modification Date:
2024-10-26 @ 1:00 PM
Study NCT ID:
NCT03788759
Status:
COMPLETED
Last Update Posted:
2022-08-29
First Post:
2018-12-20
Brief Title:
Alpha-lipoic Acid Adjunctive Therapy in Schizophrenia
Sponsor:
Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara
Organization:
Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara
Study Overview
Official Title:
Alpha-lipoic Acid Adjunctive Therapy in Schizophrenia A Randomized Double-blind Placebo-controlled Trial
Status:
COMPLETED
Status Verified Date:
2022-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Schizophrenia is a devastating mental disorder with a prevalence of approximately 1 worldwide While effective in reducing positive symptoms current treatments have limited effects on cognitive and social cognitionprocessing deficits of schizophrenia which are closely linked to real-world dysfunction and lack of socio-occupational integration There is compelling evidence for impaired antioxidant defense system and inflammatory abnormalities in schizophrenia A new therapeutic approach to the disease might well be to hinder oxidative damage inflammation and its clinical sequelae Alpha-lipoic acid ALA is a naturally occurring compound synthesized in the mitochondria that is currently approved to treat diabetic neuropathic pain Drug repurposing is a fast and cost-effective method that can overcome drug discovery challenges of targeting neuropsychiatric disorders In a pilot investigation adjunctive treatment with ALA led to robust improvement in negative and cognitive symptoms of ten patients with schizophrenia This project aims to investigate the efficacy of ALA as a disease-modifying drug for the treatment of schizophrenia by improving sociability and cognition as well as to correlate patients response with biomarkers that will shed light on the pathophysiology of this complex disease It comprises 1 a prospective randomized double-blind placebo-controlled trial to evaluate efficacy of ALA to treat cognitive and negative symptoms of patients with schizophrenia and 2 an investigation of changes in biomarkers of oxidative stress in response to adjunctive treatment with ALA The proposed study could establish a new adjunctive treatment for schizophrenia recognize a novel pharmacological approach and help unveil the biological basis of the disease
Detailed Description:
The underlying pathogenesis of schizophrenia remains unknown but aberrant reduction-oxidation has gained increasing support as an hypothesis to help explain the pathophysiology of the disease Alpha-lipoic acid ALA is a naturally occurring antioxidant essential for the function of different enzymes of mitochondrias oxidative metabolism that is currently approved to treat diabetic neuropathic pain9 ALA and its reduced form dihydrolipoic acid DHLA have important advantages over other antioxidant agents such as vitamin E and C partly due to their amphiphilic properties which confer antioxidant actions in the membrane as well as in the cytosol A preclinical study conducted in our lab showed that ALA alone and combined with clozapine reverses schizophrenia associated symptoms and pro-oxidant changes induced by ketamine in mice Before the widespread use of antipsychotics two studies found that low doses of ALA relieved symptoms in patients with schizophrenia
More recently my colleagues and I conducted an open label proof of concept study that provided encouraging evidence that low doses of ALA might be an effective adjunctive treatment for schizophrenia Based on promising preliminary results the investigators will now test ALA in a more rigorous placebo-controlled clinical study
Specific Aim1 To conduct a prospective randomized double-blind placebo-controlled trial to evaluate the efficacy of adjuvant treatment with low doses 100mg of ALA to treat cognitive and negative symptoms of patients with schizophrenia The investigators will randomize 50 patients over 4 months
Specific Aim 2 To quantify changes in biomarkers of oxidative stress in response to adjunctive treatment with ALA The hypothesis is that changes in these biomarkers will mediate the clinical response to ALA
Research Plan To carry out a proof of concept 4-month prospective randomized double-blind controlled trial of alpha-lipoic acid at doses of 100 mgday or identical placebo tablets added to ongoing antipsychotics in 50 stable patients ages 18-60 years 25 patients per group with diagnosis of schizophrenia The study will be conducted at the Drug Research and Development Center NPDM at the Universidade Federal do Ceará Fortaleza Brazil This center has a long history of performing placebocontrolled trials in clinical medicine httpwwwnpdmufcbr and has the necessary infrastructure to successfully complete the proposed study protocol All participants will give written informed consent prior to study enrollment
More recently my colleagues and I conducted an open label proof of concept study that provided encouraging evidence that low doses of ALA might be an effective adjunctive treatment for schizophrenia Based on promising preliminary results the investigators will now test ALA in a more rigorous placebo-controlled clinical study
Specific Aim1 To conduct a prospective randomized double-blind placebo-controlled trial to evaluate the efficacy of adjuvant treatment with low doses 100mg of ALA to treat cognitive and negative symptoms of patients with schizophrenia The investigators will randomize 50 patients over 4 months
Specific Aim 2 To quantify changes in biomarkers of oxidative stress in response to adjunctive treatment with ALA The hypothesis is that changes in these biomarkers will mediate the clinical response to ALA
Research Plan To carry out a proof of concept 4-month prospective randomized double-blind controlled trial of alpha-lipoic acid at doses of 100 mgday or identical placebo tablets added to ongoing antipsychotics in 50 stable patients ages 18-60 years 25 patients per group with diagnosis of schizophrenia The study will be conducted at the Drug Research and Development Center NPDM at the Universidade Federal do Ceará Fortaleza Brazil This center has a long history of performing placebocontrolled trials in clinical medicine httpwwwnpdmufcbr and has the necessary infrastructure to successfully complete the proposed study protocol All participants will give written informed consent prior to study enrollment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None