Clinical trial NCT06787781
Conditions: Metabolic Evaluation Cardiac Complications
Keywords: alphalipoic acid schizophrenia
Sponsor: University of Messina
Start date: 2021-06-01; Completion date: 2021-12-31
Enrollment: 15 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The therapeutic use of ALA in schizophrenia has recently been investigated in human populations. A case series explored the effiacy of ALA as a novel agent to treat antipsychotic-induced obesity, at a dose of 1200 mg/d (range between 600 and 1800 mg/d); reporting the key effect to be a reduction in body weight and BMI after a 12-week treatment. In a pilot open-label trial, 100 mg/d of ALA was administrated as a general adjuvant to antipsychotics therapy, with no significant improvement in BMI, abdominal circumference, blood count, or liver enzymes. Finally, another study investigated the effects of 500 mg/d of ALA on plasma adiponectin levels, fasting glucose, and aspartate aminotransferase activity, with no significant effect on the metabolic parameters. Based on this background, ALA may be a potentially interesting therapeutic agent to improve the metabolic effects of atypical antipsychotics. The purpose of this study was to assess: (1) the efficacy of ALA on metabolic factors and (2) its safety and potential therapeutic effects in a sample of schizophrenic patients in stable therapy with atypical antipsychotics.

Detailed description:

Arms: arm 1: Subject with schizophrenia administrated with ALA
Interventions: intervention 1: Alpha Lipoic Acid
Intervention descriptions: intervention 1: ALA was administrated in capsules at a xed oral daily dose of 600 mg for the entire duration of the study in addition to the atypical antipsychotic therapy.

Protocol documents:
Prot_SAP_000.pdf: 
Messina, 01.06.2021 
 
Metabolic and clinical effect of alpha-lipoic acid administration in schizophrenic subjects 
stabilized with atypical antipsychotics: A 12-week, open-label, uncontrolled study 
 
Psychiatry Unit, Polyclinic Hospital University of Messina, Via Consolare Valeria 1, Contesse, 
98125, Messina, Italy 
 
Clinical Trial number: NCT06787781 (retrospective registration) 
ID: alphalipoic1 
 
Background  
 
Management and reduction of metabolic side effects remain a major concern when considering 
atypical antipsychotics for the treatment of schizophrenia. For example, olanzapine and clozapine are 
associated with the highest risk of metabolic complications, whereas quetiapine, risperidone, 
asenapine, and amisulpride can cause moderate metabolic alterations (Carli et al., 2021). 
While there is a general consensus regarding routine monitoring of metabolic syndrome indices in 
patients receiving atypical antipsychotics, adherence to the guidelines is not common (Burghardt and 
Ellingrod, 2013) and no specific therapeutic interventions are available, meaning that metabolic 
complications in schizophrenic patients are treated as in the general population. 
Alpha lipoid acid (ALA) is a natural substance commonly found in dietary components such as 
vegetables and meats, which is an essential cofactor of mitochondrial respiratory enzymes and is 
crucial for normal functioning of oxidative metabolism (Shay et al., 2009).  
The therapeutic use of ALA in schizophrenia has recently been investigated in human populations 
and it seems to be a novel agent to treat antipsychotic-induced obesity (Kim et al., 2008). 
 
This study aimed to evaluate the efficacy of adjunctive alpha lipoid acid (ALA) in a sample of 
schizophrenia patients receiving atypical antipsychotic therapy, to assess:  
1.  the efficacy of ALA on metabolic factors  
2. its safety and potential therapeutic effects in a sample of schizophrenic patients in stable 
therapy with atypical antipsychotics. 
 
Study design 
 
12-week, open label, uncontrolled study. Alpha Lipoic Acid will be administrated in capsules at a 
fixed oral daily dose of 600 mg (Kim et al., 2008) for the entire duration of the study in addition to 
the atypical antipsychotic therapy. The drug dose will remain unchanged throughout the investigation 


and no additional medications (anti-depressant/anticonvulsant/anxiolytic/anti-inflammatory) will be 
added to their drug regimen during the study. 
Sample 
Patients who meet DSM-5 criteria for schizophrenia, in stable atypical antipsychotic monotherapy. 
Inclusion criteria 
Patients with schizophrenia, aged between 18-60 years in stable therapy with antipychotics, 
(clozapine, olanzapine, quetiapine, or risperidone) for least 3 months. 
Exclusion criteria 
Treatment with more than one atypical antipsychotic, current treatment with insulin/oral 
hypoglycaemic/lipid-lowering agents, significant concomitant medical pathologies, organic brain 
disorders, history of alcohol or substance dependence (excluding nicotine), dementia, intellectual 
disability, and pregnancy/breastfeeding. 
 
Methods  
Patients will be recruited at the University of Messina, Psychiatric Unit.  All the patients will provide 
written informed consent after a full explanation of the experimental design, according to the 
Declaration of Helsinki.  
Patients will attend two visits: initial screening (day 0), and final visit (week 12). Standard laboratory 
methods will be used to determine outcome measures.  
Primary outcome measures: fasting levels of glucose, glycated haemoglobin (Hb1c), total cholesterol, 
high-density lipoprotein (HDL) choleserol, triglycerides, and other outcome measures, including 
alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase 
(³GT), creatine phosphokinase (CPK), uric acid, creatinine, azotaemia, and prolactinaemia. 
Moreover, a physical examination will be performed to measure systolic and diastolic blood pressure, 
heart rate, body weight, and body mass index (BMI). Electrocardiography (ECG) tracing will be 
performed to measure QT interval and QTc.  
Secondary outcome measure: the assessment of psychopathologic symptoms using the Positive and 
Negative Schizophrenic Symptoms Scale (PANSS), (Kay et al., 1987).  
 
Adverse effect monitoring 
Adverse effects, either observed or spontaneously reported, will be recorded and classified for onset, 
duration, severity, and outcome. To monitor the adherence to the study protocol, weekly telephone 
calls during the study period will be carried out. 
 


Study assessment 
 
Study assessment 
Baseline 
12 weeks 
Informed consent 
x 
 
Medical history 
x 
 
Lipid and Carbohydrate blood 
parameter measurement 
x 
x 
 Hepatic 
blood 
parameter 
measurement 
x 
x 
Renal 
blood 
parameter 
measurement 
x 
x 
Body mass index 
x 
x 
Body weight  
x 
x 
Blood pressure 
x 
x 
Prolactinemia 
x 
x 
Electrocardiography 
x 
x 
 
 
Sample sizing and statistical methods for data analysis 
A power and sample size estimation were conducted (G*Power 3.1.9.2.), and under the assumption 
of an effect size of 0.8, a significant level of 0.05 with a power of 0.80, a minimal sample size of 12 
was determined. 
Statistical tests will be selected based on the available data and the specific needs that emerged during 
the analysis. Continuous data will be expressed as mean (S.D), and the within-group 
differences between baseline and final tests will be analysed by the Wilcoxon rank-sum test for 
dependent samples. As for the magnitude of the treatment effect, effect size will be calculated based 
on Cohen9s d statistic and values lower than 0.50, ranging from 0.50 to 0.79, and 0.80 or greater, will 
be considered small, moderate, and large, respectively. 
The statistical analysis will be performed using the Statistical Package for the Social Sciences (SPSS) 
25.0 software (SPSS Inc, Chicago, IL, USA). 
 
 
References 
 


1. Burghardt, K.J., Ellingrod, V.L., 2013. Detection of metabolic syndrome in schizophrenia and 
implications for antipsychotic therapy. Mol. Diagn. Ther. 17 (1), 21330. 
 
2. Shay, K.P., Moreau, R.F., Smith, E.J., Smith, A.R., Hagen, T.M., 2009. Alpha-lipoic acid as 
a dietary supplement: molecular mechanisms and therapeutic potential. Biochim. Biophys. 
Acta Gen. Subj. 1790 (10), 114931160.  
 
3. Kim, E., Park, D.-W., Choi, S.-H., Kim, J.-J., Cho, H.-S., 2008. A preliminary investigation 
of ³-lipoic acid treatment of antipsychotic drug-induced weight gain in patients with 
schizophrenia. J. Clin. Psychopharmacol. 28 (2), 1383146. 
 
4. Carli, M., Kolachalam, S., Longoni, B., Pintaudi, A., Baldini, M., Aringhieri, S., Fasciani, 
I.,Annibale, P., Maggio, R., Scarselli, M., 2021. Atypical antipsychotics and 
metabolicsyndrome: from molecular mechanisms to clinical differences. Pharmaceuticals 14 
(3), 238. 
 
5. Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The positive and negative syndrome Scale 
(PANSS) for schizophrenia. Schizophr. Bull. 13 (2), 2613276.