Pilot Study to Evaluate the Safety, Tolerability, and Efficacy of 5-ALA-Phosphate + SFC as an Immune System Enhancer Along With Vaccination Against COVID-19

An Open-Label, Pilot Study to Evaluate the Safety, Tolerability, and Efficacy of 5-ALA-Phosphate + SFC as an Immune System Enhancer Along With Vaccination Against SARS-CoV-2 Virus Infection

This is an open-label, two arm interventional exploratory study to evaluate the safety and efficacy of 5-ALA-Phosphate-SFC during the vaccination of subjects against SARS-CoV-2 (COVID-19) virus infection to define the safety and to activate the immune system during SARS-CoV-2 vaccination.

The primary objective of this study is to determine the safety of a 4 week daily oral administration of 5-ALA-Phosphate + SFC in subjects vaccinated with COVID-19 Vaccine

Study Overview

Status

Withdrawn

Conditions

Detailed Description

This is an open-label, two arm interventional exploratory study to evaluate the safety and efficacy of 5-ALA-Phosphate-SFC during the vaccination of subjects against SARS-CoV-2 (COVID-19) virus infection to define the safety and to activate the immune system during SARS-CoV-2 vaccination.

Arm 1: 100 subjects that were vaccinated with the first dose of a COVID-19 Vaccine (any brand approved in Bahrain is permitted) and that will be treated with 150mg 5-ALA Phosphate/SFC for 28 days and

Arm 2: 100 subjects that were vaccinated with the first dose of a COVID-19 Vaccine (any brand approved in Bahrain is permitted) only (Control)

The duration of this clinical study will depend on the type of the vaccine, the subject was administered with.

Primary Endpoints: All treatment emergent AEs and SAEs Grade III and IV (CTC) with reasonable possibility of causal relationship to 5-ALA-Phosphate + SFC

Secondary Endpoint:

  • Serum levels of biomarkers (CD4+/- and CD8+/- ) before and after vaccination with and without ALA/SFC administration.
  • Total antibody level and neutralizing antibody level

Exploratory Endpoints:

  1. Measurement of total IgA, IgM and IgG antibodies against SARS-CoV 2.
  2. Measurement of neutralizing antibodies against SARS-CoV-2.

Safety:

The following safety endpoints will be assessed:

  • Clinical laboratory assessments (hepatic function,)
  • All reports of AEs and SAEs Grade III and IV (CTC) with reasonable possibility of causal relationship to 5-ALA-Phosphate + SFC

Efficacy:

Efficacy will be assessing the immune system related T-helper cells and antibodies after SARS-CoV-2 vaccination for each subject.

From day 0 onwards, all subjects keep a subject diary, which they fill out daily in order to record the dosage with the study treatment. Patients must meet the testing requirements on the day of the first vaccination (Day 0) and on the Day of the second vaccination and on Day 28 and on Follow-up visit.

The food supplement 5-Aminolevulinic acid phosphate and Sodium ferrous citrate (5-ALA-Phosphate + SFC) will be administered orally daily for 4 weeks at the following TOTAL daily doses:

Subjects in the vaccination + ALA/SFC arm (Arm 1) will receive:

• In total 3 capsules of 50 mg 5-ALA-Phosphate and 28.68 mg SFC (3.04 mg as Fe) per day, 2 capsules in the morning and 1 capsule in the evening resulting in 150 mg 5-ALA-Phosphate and 86.04 mg SFC ( 9.12 mg as Fe) total daily dose for 28 days

Heme is critical for appropriate oxygen binding and delivery to remote site and without the heme contained within the hemoglobin tetramer, multicellular organisms would be unable to survive. Furthermore HO-1 degrades heme into biliverdin, carbon monoxide (CO), and iron, and biliverdin is immediately reduced and turned into bilirubin by biliverdin reductase. Biliverdin/bilirubin and CO both have anti-oxidative functions and they regulate important biological processes like inflammation, apoptosis, cell proliferation, fibrosis, and angiogenesis. Therefore, HO-1 is deemed to be a promising drug target (Ryter 2006). HO-1 is a major anti-inflammatory enzyme and a key regulator that induces immune tolerance.

5-ALA-Phosphate + SFC increases heme metabolism and HO-1 via enhancement of porphyrin biology and utilizes the HO-1 for endothelial pacification strategy. Nishio reported 2014 that 5-aminolevulinic acid, a precursor of heme, in combination with divalent iron (SFC) is also able to induce HO-1 in vitro (Nishio 2014). This was attributed to the upregulation of heme synthesis and that 5-ALA+SFC transiently increased the intracellular heme amount through the phosphorylation of ERK / p38 and the nuclear translocation of a transcription factor Nrf2, as well as the depletion of a repressor protein BACH1 binding to the promoter site of HO-1. Similarly, Nakaso et al., 2003, Nishio et al., 2014, Ogawa et al., 2001, Saito et al., 2017 found that hemin administration promoted Nrf2 nuclear translocation and BACH1 dissociation leading to HO-1 induction.

Ito found in 2018 that the combination of 5-ALA 600 mg and sodium ferrous citrate (SFC) 942 mg upregulated HO-1 in PBMC at 8 h after administration while sole administration of 5-ALA or SFC was unable to induce HO-1. HO-1 in blood myeloid and plasmacytoid dendritic cells was also upregulated by the combination of 5-ALA + SFC.

In summary the versatility of the administration of 5-ALA plus iron citrate (SFC) enables the body to counteract the inflammatory reactions that the virus induces in the endothelial system and multiple organs in the event of a virus attack by increasing the formation of HO-1.

Study Type

Interventional

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Willing and able to provide written informed consent, or with a legal representative who can provide informed consent
  • Aged ≥ 21 years (at all sites)
  • Subjects that have been vaccinated with the first dose of a vaccine (any brand approved in Bahrain is permitted) to protect against COVID-19 infection

Exclusion Criteria:

  • Subject has acute or chronic type(s) of porphyria or a family history of porphyria.
  • Subject has demonstrated previous intolerance of 5-ALA and/or SFC by topical or oral administration (except for photosensitivity)
  • Pregnant or nursing women
  • Males and females of reproductive potential who have not agreed to use an adequate method of contraception during the study.
  • Subjects who are unable or unwilling to comply with requirements of the clinical trial.
  • Participation in any other clinical trial of an experimental treatment for COVID-19
  • Subjects who may be excluded at the Investigator's discretion

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Vaccinated with 1st dose of COVID-19 Vaccine & treated with 5-ALA Phosphate/SFC
100 subjects that were vaccinated with the first dose of a COVID-19 Vaccine (any brand approved in Bahrain is permitted) and that will be treated with 150mg 5-ALA Phosphate/SFC for 28 days
The food supplement 5-Aminolevulinic acid phosphate and Sodium ferrous citrate (5-ALA-Phosphate + SFC) will be administered orally daily for 28 days. The dose will be in total 3 capsules of 50 mg 5-ALA-Phosphate and 28.68 mg SFC (3.04 mg as Fe) per day, 2 capsules in the morning and 1 capsule in the evening resulting in 150 mg 5-ALA-Phosphate and 86.04 mg SFC ( 9.12 mg as Fe).
NO_INTERVENTION: Vaccinated with 1st dose of COVID-19 Vaccine
100 subjects that were vaccinated with the first dose of a COVID-19 Vaccine (any brand approved in Bahrain is permitted) only (Control)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine the safety of a 4 week daily oral administration of 5-ALA + SFC in subject vaccinated with COVID-19 Vaccine
Time Frame: 28 days
To capture the incidence of all treatment emergent AEs and SAEs Grade III and IV (CTC) with reasonable possibility of causal relationship to 5-ALA + SFC
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the efficacy of 5-ALA + SFC in activating the immune system in subject vaccinated with COVID-19 Vaccine
Time Frame: 28 days
To determine the serum levels of biomarkers (CD4+/- and CD8+/- ) before and after vaccination with and without 5-ALA + SFC administration and total antibody level and neutralizing antibody level
28 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of total IgA, IgM and IgG antibodies against SARS-CoV 2
Time Frame: 28 days
To determine measurement of total IgA, IgM and IgG antibodies against SARS-CoV 2 before and after vaccination with and without 5-ALA + SFC administration
28 days
Clinical laboratory assessments (hepatic function)
Time Frame: 28 days
Monitoring of the liver enzymes before and during the study
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Abdulla Darwish, Dr, Bahrain Defense Force Royal Medical Services, Military Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 15, 2021

Primary Completion (ACTUAL)

August 30, 2021

Study Completion (ACTUAL)

August 30, 2021

Study Registration Dates

First Submitted

April 21, 2021

First Submitted That Met QC Criteria

April 21, 2021

First Posted (ACTUAL)

April 22, 2021

Study Record Updates

Last Update Posted (ACTUAL)

September 22, 2021

Last Update Submitted That Met QC Criteria

September 15, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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