SchizophreniaPhase 2/3NCT03788759
Alpha-lipoic Acid Adjunctive Therapy in Schizophrenia
A Phase 2/3 study testing Alpha-lipoic acid in people with Schizophrenia and Oxidative Stress, run by Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara at 1 site in Brazil.
Trial 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 cognition/processing deficits of schizophrenia, which are closely linked to real-world dysfunction and lack of… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Schizophrenia, Oxidative Stress
- What is being tested?
- Alpha-lipoic acid
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Sep 2019to 1 Dec 2021
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Capacity to provide informed consent;
- Schizophrenia diagnosis (made by research psychiatrists using the Structured Clinical Interview, SCID-5, for Diagnostic and Statistical Manual of Mental Disorders);
- Negative and/or cognitive symptoms despite adequate antipsychotic treatment;
- Ages 18-60 years
Who cannot join
- 6-month history of any drug or alcohol abuse or dependence;
- Changes in psychotropic medications within the last 4 weeks;
- Actual valproate use (potential interaction with ALA);
- General medical illness including autoimmune disorders, known chronic infections such as HIV or hepatitis C, and liver or renal failure that could adversely impact on patient outcome;
- Women who are planning to become pregnant, are pregnant, or are breastfeeding.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Núcleo de Pesquisa e Desenvolvimento de Medicamentos - UFC
Fortaleza, Ceará, 60430-275
About this study
Official title: Alpha-lipoic Acid Adjunctive Therapy in Schizophrenia: A Randomized, Double-blind, Placebo-controlled Trial
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 cognition/processing 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.
Read the 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 mitochondria's 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 mg/day 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 (http://www.npdm.ufc.br/) and has the necessary infrastructure to successfully complete the proposed study protocol. All participants will give written informed consent prior to study enrollment.
- Conditions
- Schizophrenia, Oxidative Stress
- Being tested
- Alpha-lipoic acid, Placebo Oral Tablet
- Keywords
- Schizophrenia, Drug repurposing, Alpha-lipoic acid, Adjuvant treatment
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alpha-lipoic acidDrug
Administration of ALA (100 mg/day) for 4 months, as an adjunct to antipsychotic medication.
Placebo Oral TabletDrug
Administration of placebo, as an adjunct to antipsychotic medication.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | 25 subjects will be randomized to 100mg of alpha-lipoic acid. Receives: Drug: Alpha-lipoic acid |
| Placebo group | Placebo comparator | 25 subjects will be randomized to placebo. Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the Brief Psychiatry Rating Scale (BPRS) scores
18-item rating scale to assess changes in psychopathology; each item is scored 0-6, yielding a total between 0 and 108.
Measured: Baseline and 16 weeks
Secondary outcomes (34)
Change in the Simpson-Angus Extrapyramidal Symptoms Scale (SAS) scores
10-item rating scale to assess extrapyramidal symptoms; each item is scored 0-4, yielding a total between 0 and 40.
Measured: Baseline and 16 weeks
Brain resting state activity
Functional Magnetic Resonance Imaging (fMRI) scans before and after treatment
Measured: Baseline and 16 weeks
Gut Microbiota Composition
Analyses of patient's gut microbiota
Measured: Baseline and 16 weeks
Change in Body Mass Index (BMI)
Weight and height will be combined to report BMI in kg/m^2
Measured: Baseline and 16 weeks
Change in Abdominal Circumference
Abdominal Circumference in cm
Measured: Baseline and 16 weeks
Change in plasma Aspartate Aminotransferase (AST)
AST in U/L
Measured: Baseline and 16 weeks
Change in plasma Aspartate Aminotransferase (AST) Alanine Aminotransferase (ALT)
ALT in U/L
Measured: Baseline and 16 weeks
Change in Hemoglobin concentration (HC)
HC in g/dL
Measured: Baseline and 16 weeks
Change in Hematocrit (Ht)
Ht in %
Measured: Baseline and 16 weeks
Change in White blood cell count (WBC)
WBC in number per microliter
Measured: Baseline and 16 weeks
Change in Neutrophil Count (NC)
NC in number per microliter
Measured: Baseline and 16 weeks
Change in Platelet Count (PC)
PC in number per microliter
Measured: Baseline and 16 weeks
Change in Glycohemoglobin (HbA1c)
HbA1c in %
Measured: Baseline and 16 weeks
Change in serum level of Vitamin B12
Vitamin B12 in pg/mL
Measured: Baseline and 16 weeks
Change in serum level of Folic Acid
Folic Acid in ng/mL
Measured: Baseline and 16 weeks
Change in Plasma Glutathione (GSH)
GSH in ng/mL
Measured: Baseline and 16 weeks
Change in serum level of Nitrite
Nitrite in nanomole/mililiter
Measured: Baseline and 16 weeks
Change in serum level of Thiobarbituric acid reactive substances (TBARS)
TBARS in mmol of malonaldehyde/mL
Measured: Baseline and 16 weeks
Change in serum level of Interleukin 1 β (IL-1β)
IL-1β in pg/mL
Measured: Baseline and 16 weeks
Change in serum level of Interleukin-4
IL-4 in pg/mL
Measured: Baseline and 16 weeks
Change in serum level of Interferon gamma (IFNγ)
IFNγ in pg/mL
Measured: Baseline and 16 weeks
Change in serum level of Tumor necrosis factor alpha (TNF-α)
TNF-α in pg/mL
Measured: Baseline and 16 weeks
Change in Indoleamine 2,3-dioxygenase (IDO) enzymatic activity
IDO activity in U IDO mol^-1/mg^-1
Measured: Baseline and 16 weeks
Change in serum level of Eotaxin
Eotaxin in ng/mL
Measured: Baseline and 16 weeks
Change in serum level of Isoprostanes
Isoprostanes in pg/mL
Measured: Baseline and 16 weeks
Change in serum level of Calprotectin
Serum Calprotectin in ng/mL
Measured: Baseline and 16 weeks
Change in serum level of Serotonin
Serotonin in ng/mL
Measured: Baseline and 16 weeks
Change in Block Corsi Test
This test assesses visuo-spatial short term working memory. Participants are asked to mimick a researcher as he/she taps a sequence of up to nine identical spatially separated blocks. The test measures both the number of correct sequences and the longest sequence remembered.
Measured: Baseline and 16 weeks
Change in serum level of Tryptophan
Tryptophan in micrograms/mL
Measured: Baseline and 16 weeks
Change in Trail Making Test
Trail Making Test measured in time and number of errors. It tests visual attention and task switching. It consists of two parts in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. Provide information about visual search speed, scanning, speed of processing, mental flexibility, executive functioning.
Measured: Baseline and 16 weeks
Change in Subtest Digit Span
Individual tries to repeat digits forward, backward, and in ascending order. This test measures short term memory, working memory. The score is the maximum number of digits correctly remembered.
Measured: Baseline and 16 weeks
Category (Animal) Fluency
Participants have to produce as many words as possible from a category in a given time (usually 60 seconds). Performance measure is the total number of words
Measured: Baseline and 16 weeks
F-A-S test
It assesses phonemic fluency by requesting an individual to orally produce as many words as possible that begin with the letters F, A, and S within a prescribed time frame, usually 1 min.
Measured: Baseline and 16 weeks
Rey Auditory Verbal Learning Test
Participants are asked to repeat list of 15 unrelated words; another list of 15 unrelated words are given and participants must again repeat the original list of 15 words and then again after 30 minutes. Score range: 0-15
Measured: Baseline and 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2018
- Study start1 Sep 2019
- Primary completion1 Dec 2021
- Study completion1 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Proof of concept 4-month prospective, randomized, double-blind, controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara
- Sponsor type
- University, hospital or other
- Collaborators
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Responsible party
- Principal investigator, Lia Sanders, Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara
- Investigators
- Lia LO Sanders, MD, PhD, Principal investigator, Núcleo de Pesquisa e Desenvolvimento de Medicamentos
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03788759
- Sponsor's protocol ID
- LipoicStudy
- Status last verified
- Aug 2022
- First submitted
- 20 Dec 2018
- Last updated
- 29 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Perala J, Suvisaari J, Saarni SI, Kuoppasalmi K, Isometsa E, Pirkola S, Partonen T, Tuulio-Henriksson A, Hintikka J, Kieseppa T, Harkanen T, Koskinen S, Lonnqvist J. Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry. 2007 Jan;64(1):19-28. doi: 10.1001/archpsyc.64.1.19.
PubMed 17199051Foussias G, Agid O, Fervaha G, Remington G. Negative symptoms of schizophrenia: clinical features, relevance to real world functioning and specificity versus other CNS disorders. Eur Neuropsychopharmacol. 2014 May;24(5):693-709. doi: 10.1016/j.euroneuro.2013.10.017. Epub 2013 Nov 11.
PubMed 24275699Reddy RD, Yao JK. Free radical pathology in schizophrenia: a review. Prostaglandins Leukot Essent Fatty Acids. 1996 Aug;55(1-2):33-43. doi: 10.1016/s0952-3278(96)90143-x.
PubMed 8888121Bitanihirwe BK, Woo TU. Oxidative stress in schizophrenia: an integrated approach. Neurosci Biobehav Rev. 2011 Jan;35(3):878-93. doi: 10.1016/j.neubiorev.2010.10.008. Epub 2010 Oct 23.
PubMed 20974172Gysin R, Kraftsik R, Boulat O, Bovet P, Conus P, Comte-Krieger E, Polari A, Steullet P, Preisig M, Teichmann T, Cuenod M, Do KQ. Genetic dysregulation of glutathione synthesis predicts alteration of plasma thiol redox status in schizophrenia. Antioxid Redox Signal. 2011 Oct 1;15(7):2003-10. doi: 10.1089/ars.2010.3463. Epub 2010 Oct 30.
PubMed 20673128Fournier M, Ferrari C, Baumann PS, Polari A, Monin A, Bellier-Teichmann T, Wulff J, Pappan KL, Cuenod M, Conus P, Do KQ. Impaired metabolic reactivity to oxidative stress in early psychosis patients. Schizophr Bull. 2014 Sep;40(5):973-83. doi: 10.1093/schbul/sbu053. Epub 2014 Mar 31.
PubMed 24687046Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffin JL, Wayland M, Freeman T, Dudbridge F, Lilley KS, Karp NA, Hester S, Tkachev D, Mimmack ML, Yolken RH, Webster MJ, Torrey EF, Bahn S. Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry. 2004 Jul;9(7):684-97, 643. doi: 10.1038/sj.mp.4001511.
PubMed 15098003Vallianou N, Evangelopoulos A, Koutalas P. Alpha-lipoic Acid and diabetic neuropathy. Rev Diabet Stud. 2009 Winter;6(4):230-6. doi: 10.1900/RDS.2009.6.230. Epub 2009 Dec 30.
PubMed 20043035Scott BC, Aruoma OI, Evans PJ, O'Neill C, Van der Vliet A, Cross CE, Tritschler H, Halliwell B. Lipoic and dihydrolipoic acids as antioxidants. A critical evaluation. Free Radic Res. 1994 Feb;20(2):119-33. doi: 10.3109/10715769409147509.
PubMed 7516789Vasconcelos GS, Ximenes NC, de Sousa CN, Oliveira Tde Q, Lima LL, de Lucena DF, Gama CS, Macedo D, Vasconcelos SM. Alpha-lipoic acid alone and combined with clozapine reverses schizophrenia-like symptoms induced by ketamine in mice: Participation of antioxidant, nitrergic and neurotrophic mechanisms. Schizophr Res. 2015 Jul;165(2-3):163-70. doi: 10.1016/j.schres.2015.04.017. Epub 2015 Apr 30.
PubMed 25937462GIAMATTEI L. [Thioctic acid in therapy of schizophrenia]. Osp Psichiatr. 1957 Apr-Jun;25(2):221-8. No abstract available. Italian.
PubMed 13526963ALTSCHULE MD, GONCZ RM, HOLLIDAY PD. Carbohydrate metabolism in brain disease. XI. Effects of thioctic (alpha-lipoic) acid in chronic schizophrenia. AMA Arch Intern Med. 1959 May;103(5):726-9. doi: 10.1001/archinte.1959.00270050048008. No abstract available.
PubMed 13636491Emsley R, Chiliza B, Asmal L, du Plessis S, Phahladira L, van Niekerk E, van Rensburg SJ, Harvey BH. A randomized, controlled trial of omega-3 fatty acids plus an antioxidant for relapse prevention after antipsychotic discontinuation in first-episode schizophrenia. Schizophr Res. 2014 Sep;158(1-3):230-5. doi: 10.1016/j.schres.2014.06.004. Epub 2014 Jul 2.
PubMed 24996507Kim E, Park DW, Choi SH, Kim JJ, Cho HS. A preliminary investigation of alpha-lipoic acid treatment of antipsychotic drug-induced weight gain in patients with schizophrenia. J Clin Psychopharmacol. 2008 Apr;28(2):138-46. doi: 10.1097/JCP.0b013e31816777f7.
PubMed 18344723Seybolt SE. Less is more. Schizophr Res. 2014 Dec;160(1-3):222-3. doi: 10.1016/j.schres.2014.10.022. Epub 2014 Oct 31. No abstract available.
PubMed 25458573
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alpha-lipoic Acid Adjunctive Therapy in Schizophrenia: A Randomized, Double-blind, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT03788759
- Acronym / sponsor ID
- LipoicStudy
- Conditions
- Schizophrenia, Oxidative Stress
- Keywords
- Schizophrenia, Drug repurposing, Alpha-lipoic acid, Adjuvant treatment
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do CearaUniversity, hospital or other
- Collaborators
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 1 Dec 2021 (actual)
- Study completion
- 1 Dec 2021 (actual)
- First posted
- 28 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 cognition/processing 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 mitochondria's 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 mg/day 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 (http://www.npdm.ufc.br/) and has the necessary infrastructure to successfully complete the proposed study protocol. All participants will give written informed consent prior to study enrollment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Proof of concept 4-month prospective, randomized, double-blind, controlled trial
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Drug: Alpha-lipoic acid25 subjects will be randomized to 100mg of alpha-lipoic acid. |
| Placebo group | Placebo comparator | Drug: Placebo Oral Tablet25 subjects will be randomized to placebo. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Capacity to provide informed consent;
- Schizophrenia diagnosis (made by research psychiatrists using the Structured Clinical Interview, SCID-5, for Diagnostic and Statistical Manual of Mental Disorders);
- Negative and/or cognitive symptoms despite adequate antipsychotic treatment;
- Ages 18-60 years
Key exclusion criteria (5 listed)
- 6-month history of any drug or alcohol abuse or dependence;
- Changes in psychotropic medications within the last 4 weeks;
- Actual valproate use (potential interaction with ALA);
- General medical illness including autoimmune disorders, known chronic infections such as HIV or hepatitis C, and liver or renal failure that could adversely impact on patient outcome;
- Women who are planning to become pregnant, are pregnant, or are breastfeeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alpha-lipoic acidAdministration of ALA (100 mg/day) for 4 months, as an adjunct to antipsychotic medication. | Drug | Experimental group |
| Placebo Oral TabletAdministration of placebo, as an adjunct to antipsychotic medication. | Drug | Placebo group |
Primary outcome
Change in the Brief Psychiatry Rating Scale (BPRS) scores
Time frame: Baseline and 16 weeks
18-item rating scale to assess changes in psychopathology; each item is scored 0-6, yielding a total between 0 and 108.
34 secondary outcomes
Change in the Simpson-Angus Extrapyramidal Symptoms Scale (SAS) scores
Time frame: Baseline and 16 weeks
Brain resting state activity
Time frame: Baseline and 16 weeks
Gut Microbiota Composition
Time frame: Baseline and 16 weeks
Change in Body Mass Index (BMI)
Time frame: Baseline and 16 weeks
Change in Abdominal Circumference
Time frame: Baseline and 16 weeks
Change in plasma Aspartate Aminotransferase (AST)
Time frame: Baseline and 16 weeks
Change in plasma Aspartate Aminotransferase (AST) Alanine Aminotransferase (ALT)
Time frame: Baseline and 16 weeks
Change in Hemoglobin concentration (HC)
Time frame: Baseline and 16 weeks
Change in Hematocrit (Ht)
Time frame: Baseline and 16 weeks
Change in White blood cell count (WBC)
Time frame: Baseline and 16 weeks
Change in Neutrophil Count (NC)
Time frame: Baseline and 16 weeks
Change in Platelet Count (PC)
Time frame: Baseline and 16 weeks
Change in Glycohemoglobin (HbA1c)
Time frame: Baseline and 16 weeks
Change in serum level of Vitamin B12
Time frame: Baseline and 16 weeks
Change in serum level of Folic Acid
Time frame: Baseline and 16 weeks
Change in Plasma Glutathione (GSH)
Time frame: Baseline and 16 weeks
Change in serum level of Nitrite
Time frame: Baseline and 16 weeks
Change in serum level of Thiobarbituric acid reactive substances (TBARS)
Time frame: Baseline and 16 weeks
Change in serum level of Interleukin 1 β (IL-1β)
Time frame: Baseline and 16 weeks
Change in serum level of Interleukin-4
Time frame: Baseline and 16 weeks
Change in serum level of Interferon gamma (IFNγ)
Time frame: Baseline and 16 weeks
Change in serum level of Tumor necrosis factor alpha (TNF-α)
Time frame: Baseline and 16 weeks
Change in Indoleamine 2,3-dioxygenase (IDO) enzymatic activity
Time frame: Baseline and 16 weeks
Change in serum level of Eotaxin
Time frame: Baseline and 16 weeks
Change in serum level of Isoprostanes
Time frame: Baseline and 16 weeks
Change in serum level of Calprotectin
Time frame: Baseline and 16 weeks
Change in serum level of Serotonin
Time frame: Baseline and 16 weeks
Change in Block Corsi Test
Time frame: Baseline and 16 weeks
Change in serum level of Tryptophan
Time frame: Baseline and 16 weeks
Change in Trail Making Test
Time frame: Baseline and 16 weeks
Change in Subtest Digit Span
Time frame: Baseline and 16 weeks
Category (Animal) Fluency
Time frame: Baseline and 16 weeks
F-A-S test
Time frame: Baseline and 16 weeks
Rey Auditory Verbal Learning Test
Time frame: Baseline and 16 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2022.
- Background: PubMed 17199051Perala J, Suvisaari J, Saarni SI, Kuoppasalmi K, Isometsa E, Pirkola S, Partonen T, Tuulio-Henriksson A, Hintikka J, Kieseppa T, Harkanen T, Koskinen S, Lonnqvist J. Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry. 2007 Jan;64(1):19-28. doi: 10.1001/archpsyc.64.1.19.
- Background: PubMed 24275699Foussias G, Agid O, Fervaha G, Remington G. Negative symptoms of schizophrenia: clinical features, relevance to real world functioning and specificity versus other CNS disorders. Eur Neuropsychopharmacol. 2014 May;24(5):693-709. doi: 10.1016/j.euroneuro.2013.10.017. Epub 2013 Nov 11.
- Background: PubMed 8888121Reddy RD, Yao JK. Free radical pathology in schizophrenia: a review. Prostaglandins Leukot Essent Fatty Acids. 1996 Aug;55(1-2):33-43. doi: 10.1016/s0952-3278(96)90143-x.
- Background: PubMed 20974172Bitanihirwe BK, Woo TU. Oxidative stress in schizophrenia: an integrated approach. Neurosci Biobehav Rev. 2011 Jan;35(3):878-93. doi: 10.1016/j.neubiorev.2010.10.008. Epub 2010 Oct 23.
- Background: PubMed 20673128Gysin R, Kraftsik R, Boulat O, Bovet P, Conus P, Comte-Krieger E, Polari A, Steullet P, Preisig M, Teichmann T, Cuenod M, Do KQ. Genetic dysregulation of glutathione synthesis predicts alteration of plasma thiol redox status in schizophrenia. Antioxid Redox Signal. 2011 Oct 1;15(7):2003-10. doi: 10.1089/ars.2010.3463. Epub 2010 Oct 30.
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- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lia LO Sanders, MD, PhD principal investigator
Núcleo de Pesquisa e Desenvolvimento de Medicamentos
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Alpha-lipoic acid in people with Schizophrenia and Oxidative Stress, run by Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the Brief Psychiatry Rating Scale (BPRS) scores (time frame: Baseline and 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03788759, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2022.