Alpha-Lipoic Acid in Patients With Sepsis

Sponsor

Ain Shams University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05808946

Collaborator

(none)

Enrollment

Location

Arms

18.8

Anticipated Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Alpha-lipoic acid (ALA) is a powerful antioxidant that can help reduce the harmful effects of free radicals in the body. When the body is fighting sepsis, the immune response generates a lot of free radicals that can damage cells and tissues. ALA can neutralize these free radicals, reducing oxidative stress and preventing damage to cells and tissues.

ALA also has anti-inflammatory properties, meaning it can reduce inflammation in the body. Inflammation is a key feature of sepsis, and it can cause damage to organs and tissues. By reducing inflammation, ALA can help prevent damage to organs and tissues, reducing the risk of sepsis complications such as organ failure.

The objective of this research is to investigate the impact of ALA on individuals who have sepsis. The study will involve dividing the participants into two groups: a control group and an ALA group. The control group will receive the standard supportive care for sepsis management. Meanwhile, the ALA group will receive 1200 mg of ALA daily in addition to the standard care.

Condition or Disease	Intervention/Treatment	Phase
Sepsis	Drug: Alpha-Lipoic Acid Drug: Sepsis Supportive Care	Phase 2/Phase 3

Detailed Description

Sepsis is considered a leading cause of death in hospitals and intensive care units (ICU) due to the body's excessive response to the invading pathogen, resulting in severe inflammation and oxidative stress. As a result, it is postulated that administering anti-inflammatory and antioxidant agents may have potential benefits on the clinical outcomes of patients with sepsis. Alpha-lipoic acid, a nutraceutical with both potent anti-inflammatory and antioxidant properties, could be a potential treatment option. Several animal models showed positive results when using ALA in septic rats. Hence, it might be a potential candidate for improving the clinical outcome in septic patients. Thus, the aim of this study is to evaluate the efficacy and safety of alpha-lipoic acid when administered at a dose of 1200 mg/day in septic patients.

This trial is a prospective randomized-controlled open label trial where a total number of 60 patients will be enrolled in the study. They will be randomized using simple randomization into the control group and the treatment group with a ratio of 1 to 1 (30 patients in each group). The control group will receive the standard supportive care of sepsis management. Supportive care typically involves a combination of interventions to stabilize the patient's condition and manage their symptoms such as administration of intravenous fluids (e.g.: normal saline) and appropriate antibiotics. Additionally, oxygen therapy, mechanical ventilation, and vasopressors (e.g.: norepinephrine or dobutamine) may be provided on an as-needed basis to support breathing and maintain blood pressure. Meanwhile, the ALA group will be given 1200 mg of ALA daily in addition to the standard care.

The efficacy of ALA will be assessed by tracking the mortality rates of enrolled patients during their hospital stay and 28 days after, as well as the duration of their ICU and hospital stay. The Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, C-reactive protein (CRP), Total Leukocytic Count (TLC), and plasma monocyte chemoattractant protein 1 (MCP-1) will also be measured at baseline and regularly during the study to evaluate ALA's impact on sepsis. Also, the need for mechanical ventilation and vasopressors will be recorded as an indicator of ALA's efficacy. The safety of ALA will be determined by monitoring the patients for any adverse effects that may occur due to the drug such as nausea or itching.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Effect of Alpha-Lipoic Acid on the Clinical Outcome of Patients With Sepsis

Actual Study Start Date :

Mar 10, 2023

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alpha-Lipoic Acid Group	Drug: Alpha-Lipoic Acid 1200 mg of ALA daily (given as two 600 mg capsules once daily) Other Names: Thioctic Acid Drug: Sepsis Supportive Care Appropriate IV fluid, Appropriate antibiotic, Vasopressors if needed, Mechanical ventilation if needed Other Names: Sepsis Management
Active Comparator: Control Group	Drug: Sepsis Supportive Care Appropriate IV fluid, Appropriate antibiotic, Vasopressors if needed, Mechanical ventilation if needed Other Names: Sepsis Management

Arm

Intervention/Treatment

Experimental: Alpha-Lipoic Acid Group

Drug: Alpha-Lipoic Acid

1200 mg of ALA daily (given as two 600 mg capsules once daily)

Other Names:

Thioctic Acid

Drug: Sepsis Supportive Care

Appropriate IV fluid, Appropriate antibiotic, Vasopressors if needed, Mechanical ventilation if needed

Other Names:

Sepsis Management

Active Comparator: Control Group

Drug: Sepsis Supportive Care

Appropriate IV fluid, Appropriate antibiotic, Vasopressors if needed, Mechanical ventilation if needed

Other Names:

Sepsis Management

Outcome Measures

Primary Outcome Measures

Mortality [28 days since patient enrollment in the study]
The patient will be followed-up for mortality rate during hospital stay and up to 28 days.

Secondary Outcome Measures

Plasma MCP-1 [Plasma samples will be collected on days 1, 3 and 7 for each patient enrolled]
Monocyte chemoattractant protein-1 (MCP-1) will be assessed in each patient as an inflammatory marker.
SOFA score [Assessed on day 1, 3 and 7 and then every 3 days till patient is discharged or death occurs, up to maximum 28 days.]
A scoring system used to measure the extent of organ dysfunction/failure in critically ill patients. The score is calculated based on six different parameters: respiratory (PaO2/FiO2 ratio), cardiovascular (mean arterial pressure (MAP)), hepatic (serum bilirubin level), coagulation (platelet count), renal (serum creatinine level and urine output), and neurological (Glasgow Coma Scale). This makes the SOFA score a composite outcome.
Length of ICU stay [28 days]
The total duration of ICU stay will be estimated for each patient.
Length of hospital stay [28 days]
The total duration of hospital stay will be estimated for each patient.
Need for Mechanical Ventilation [28 days]
Number of patients requiring mechanical ventilation will be recorded along with the duration of ventilation
Need for Vasopressors [28 days]
Number of patients requiring vasopressors as norepinephrine or dopamine will be recorded along with the dose and the duration of vasopressor administration
Adverse Effects of Alpha-Lipoic Acid [28 days]
All adverse effects experienced by the participants will be recorded in both arms. Expected side effects include gastrointestinal side effects (e.g.: nausea and vomiting) and hypersensitivity of the skin (e.g.: urticaria and itching sensation).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients 18 years or older
Patients able to receive oral or enteral medication
Patients with confirmed diagnosis of sepsis according to Sepsis-3 definition; documented or suspected infection associated with organ dysfunction identified by acute change in total SOFA score of 2 points or more.

Exclusion Criteria:

Patients with septic shock defined as patients with sepsis who has persistent hypotension that necessitates the use of vasopressors to maintain MAP greater than or equal to 65mmHg and a blood lactate level greater than 2 mmol/L (18 mg/dL) despite absence of hypovolemia.
Patients on mechanical ventilation at baseline.
Pregnant women
Patients already receiving ALA supplementation before ICU admission