SARS-CoV 2NCT04542850
Pilot Study to Evaluate the Safety, Tolerability, and Efficacy of 5-ALA-Phosphate + SFC in Subjects With COVID-19
A study testing 5-ALA-Phosphate + SFC (5-ALA + SFC) in people with SARS-CoV 2 and COVID-19, run by Royal College of Surgeons in Ireland - Medical University of Bahrain at 2 sites in Bahrain.
Trial summary
This is an open-label, interventional exploratory study to evaluate the safety and efficacy of 5-ALA-Phosphate + SFC in subjects with acute moderate or severe respiratory illness secondary to infection with SARS-CoV-2 virus (COVID-19) involving 40 subjects. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- SARS-CoV 2, COVID-19
- What is being tested?
- 5-ALA-Phosphate + SFC (5-ALA + SFC)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 2 sitesBahrain
- Study dates
- 15 Nov 2020to 28 Oct 2021
- Phase
- Interventional
- 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 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent, or with a legal representative who can provide informed consent
- Aged ≥ 21 to 70 years
- Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test before beginning study dose regime
- qSOFA ≥ 1
- Currently hospitalized
- Moderate COVID-19 patients should meet any of the following criteria:
Show all 10Show fewer
- evidence of lower respiratory disease by clinical assessment (qSOFA ≥ 1or imaging) and saturation of oxygen (SpO2) ≥94% on room air at sea level.
- Severe COVID-19 patients should meet any of the following criteria: a respiratory frequency >30 breaths per minute, SpO2 <94% on room air at sea level, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mmHg, and lung infiltrates >50% (if possible to measure). In exceptional cases the investigator can decide due to certain signs and symptoms to assign a moderate patient to the severe group although not all criteria mentioned before are fulfilled (to be documented with explanation).
- Radiographic evidence (chest X-ray or chest CT scan) of pulmonary infiltrates
- Able to swallow 5 capsules of study product at dosing time points.
Who cannot join
- Subject has critical symptoms of COVID19 infection as defined as: high-flow oxygen therapy (>15 l/min delivered by nasal cannula or mask) or invasive mechanical ventilation signifying respiratory failure, septic shock, and/or multiple organ dysfunction ventilation at screening.
- Subject is nourished via a nasogastric tube
- 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
Show all 13Show fewer
- adequate method of contraception during the study For females, adequate birth control methods will be defined as: hormonal contraceptives, intrauterine device or double barrier contraception, i.e., condom + diaphragm, condom or diaphragm + spermicidal gel or foam For males, adequate birth control methods will be defined as double barrier contraception, i.e., condom + diaphragm, condom or diaphragm + spermicidal gel or foam For females, menopause is defined as one year without menses; if in question, a folliclestimulating hormone of >40 U/ml must be documented. Hysterectomy, bilateral oophorectomy,or bilateral tubal ligation must be documented, as applicable
- 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
- Evidence of multiorgan failure
- Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 X upper limit of normal (ULN)
- Creatinine clearance < 50 mL/min using the Cockcroft-Gault formula for participants ≥ 18 years of age {Cockcroft 1976}
- Any other reason that makes the subject unsuitable in the Investigator's opinion
Trial locations and contacts
2 sites in 1 country.
Bahrain2 sites
Bahrain Defense Force Royal Medical Services, Military Hospital
Manama
Salmaniya Medical Complex
Manama
About this study
Official title: An Open-Label, Pilot Study to Evaluate the Safety, Tolerability, and Efficacy of 5-Aminolevulinic Acid Phosphate and Sodium Ferrous Citrate (5-ALA-Phosphate + SFC) in Subjects With SARS-CoV-2 Infection (COVID-19)
This is an open-label, interventional exploratory study to evaluate the safety and efficacy of 5-ALA-Phosphate + SFC in subjects with acute moderate or severe respiratory illness secondary to infection with SARS-CoV-2 virus (COVID-19) involving 40 subjects.
The primary objective is to evaluate the safety of 4-week oral administration of 5-ALAPhosphate + SFC. This study is expected to last for 4 weeks and will include follow-up until day 28 in the hospital or in an outpatient setting if the subjects are discharged earlier.
Read the detailed description
This is an open-label, interventional exploratory study to evaluate the safety and efficacy of 5-ALA-Phosphate + SFC in subjects with acute moderate or severe respiratory illness secondary to infection with SARS-CoV-2 virus (COVID-19).
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.
The primary endpoints of this study is- all treatment emergent AEs and SAEs Grade III and IV (CTC) with reasonable possibility of causal relationship to 5-ALA-Phosphate + SFC. 40 subjects with symptoms requiring hospitalization will be enrolled in thestudy, with 20 subjects enrolled in each group below:
Group 1: 20 Moderately ill hospitalized subjects not requiring assisted ventilation Group 2: 20 Severely ill hospitalized subjects requiring assisted ventilation
The duration of this clinical study will be 4 weeks, and follow-up will be performed until Day 28 in hospital, or in an outpatient setting if subjects improve and are discharged home or to alternative care facility.
- Conditions
- SARS-CoV 2, COVID-19
- Being tested
- 5-ALA-Phosphate + SFC (5-ALA + SFC)
- Keywords
- 5-ALAPhosphate + SFC, COVID-19
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-ALA-Phosphate + SFC (5-ALA + SFC)Dietary supplement
Moderately ill hospitalized patients will receive:
250 mg 5-ALA-Phosphate and 143.4 mg SFC (15.2 mg as Fe) two times daily (resulting in 500 mg 5-ALA-Phosphate and 286.8 mg SFC (30.4 mg as Fe) daily) for 7 days, then 250 mg 5-ALA-Phosphate and 143.4 mg SFC (15.2 mg as Fe) once daily for 21 days
Severely ill hospitalized patients will receive:
250 mg 5-ALA-Phosphate and 143.4 mg SFC (15.2 mg as Fe) three times daily (resulting in 750 mg 5-ALA-Phosphate and 430.2 mg SFC (45.6 mg as Fe) daily) for 7 days, then 250 mg 5-ALA-Phosphate and 143.4 mg SFC (15.2 mg as Fe) once daily for 21 days
| Study group | Role | What they receive |
|---|---|---|
| Moderate group and Severe Group | Other | Moderate group and Severe group - . Both groups will be administered 5-aminolevulinic acid (5-ALA) is a natural delta amino acid widely present in nature that can be found in common food. 5-ALA combined with sodium ferrous citrate (SFC) produces the nutritional dietary supplement 5-ALA-Phosphate + SFC (5-ALA + SFC). Receives: Dietary Supplement: 5-ALA-Phosphate + SFC (5-ALA + SFC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of treatment emergent Adverse Events (safety and tolerability) of 5-ALA-Phospate + SFC in patients with acute moderate or severe respiratory illness secondary to infection with SARS-CoV-2 virus (COVID-19).
To describe the incidence of treatment-emergent Adverse Events (TEAEs) of CTC Grades III and IV within four weeks following base line dose.
Measured: 28 days
Secondary outcomes (49)
Sum COVID-19 Modified Ordinal Scale for Clinical Improvement maximum daily score over 28 days of dosing for Moderate group and for Severe group
To describe patient's condition in Moderate and Severe group using average, median, minimum and maximum in COVID-19 Modified Ordinal Scale for Clinical Improvement score.
Measured: 28 days
Rate of change in COVID-19 Modified Ordinal Scale for Clinical Improvement maximum daily score over 28 days of dosing for individual subjects in Moderate group and in Severe group
To describe patient´s condition in Moderate and Severe Group using rate of change in COVID-19 Modified Ordinal Scale for Clinical Improvement score.
Measured: 28 days
Patient and subgroup profile of COVID-19 Modified Ordinal Scale for Clinical Improvement score vs. days hospitalized
To describe patient´s condition in Moderate and Severe Group using patient and subgroup profile of COVID-19 Modified Ordinal Scale for Clinical Improvement score vs. days hospitalized.
Measured: 28 days
Overall survival
To describe time until death from any cause
Measured: day 14 and day 28
Results of investigator´s assessment of patient´s oxygen therapy
To describe patient´s blood oxygenation
Measured: 28 days
Results of mechanical ventilation settings
To describe mechanical ventilation settings course during study.
Measured: 28 days
Results of duration of ventilation
To describe duration of patient´s ventilation
Measured: from date of enrolment until the extubation or until last 5-ALA- Phosphate -SFC administration on day 28
The time to resolution of patient´s symptoms
To describe patient´s specific symptoms course during study.
Measured: 28 days
Results of patient´s oxygen saturation (respiratory parameters)
To describe patient´s oxygen saturation course during study.
Measured: 28 days
Length of hospitalization
To describe duration of hospitalization in the patient groups.
Measured: From date of enrolment until last 5-ALA- Phosphate -SFC administration at day 28
The total time in ICU
To describe duration of residence in ICU in the patient groups.
Measured: From date of enrolment until last 5-ALA- Phosphate -SFC administration at day 28
Results of investigator´s assessment of patient´s condition using (q)SOFA score
To describe patient´s (q)SOFA score course during study.
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s PT parameter
To describe patient´s coagulation function course during study which by evaluating the PT value.
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s D-Dimer parameter
To describe patient´s coagulation function course during study which by evaluating the D-Dimer value.
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s PTT parameter
To describe patient´s coagulation function course during study which by evaluating the PTT value.
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s SARS-CoV-2 viral load status (efficacy)
To describe patient's SARS-CoV-2 viral load course during study.
Measured: day 7, 14 and 28
Results of patient´s Procalcitonin level.
To describe infection parameter course of each patient during study by evaluating the Procalcitonin value.
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s IL-6 level
To describe infection parameter course of each patient during study by evaluating the IL-6 value.
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s Serum Ferritin level
To describe infection parameter course of each patient during study by evaluating the Serum ferritin value.
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s C-Reactive protein (CRP) level
To describe infection parameter course of each patient during study by evaluating the C-Reactive protein (CRP) value.
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s T helper cells (CD4/CD8) level.
To describe infection parameter course of each patient during study by evaluating the T helper cells (CD4/CD8) value.
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s Bilirubin level.
To describe infection parameter course of each patient during study by evaluating the Bilirubin value.
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Leucocytes
To describe laboratory assessments course during study by evaluating Leucocytes value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Neutrophils
To describe laboratory assessments course during study by evaluating Neutrophils value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Lymphocyte
To describe laboratory assessments course during study by evaluating Lymphocyte value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Platelets
To describe laboratory assessments course during study by evaluating Platelets value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Hemoglobin
To describe laboratory assessments course during study by evaluating Hemoglobin value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Albumin
To describe laboratory assessments course during study by evaluating Albumin value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s AST
To describe laboratory assessments course during study by evaluating AST value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s ALT
To describe laboratory assessments course during study by evaluating ALT value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Total bilirubin
To describe laboratory assessments course during study by evaluating Total bilirubin value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Blood urea nitrogen
To describe laboratory assessments course during study by evaluating Blood urea nitrogen value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Serum creatinine
To describe laboratory assessments course during study by evaluating Serum creatinine value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Creatinine kinase
To describe laboratory assessments course during study by evaluating Creatinine kinase value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s LDH
To describe laboratory assessments course during study by evaluating LDH value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Myoglobin glucose
To describe laboratory assessments course during study by evaluating Myoglobin glucose value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s aPTT
To describe laboratory assessments course during study by evaluating aPTT value
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s urine
To describe laboratory assessments course during study by evaluating urinalysis (urine test strip)
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on hepatic function
To describe laboratory assessments course during study by evaluating hepatic function
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s renal function
To describe laboratory assessments course during study by evaluating renal function
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s iron parameters
To describe laboratory assessments course during study by evaluating iron parameters
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s physical examination
To describe patient´s conditions course during study using physical examination which include General Appearance, ENT, Respiratory, Cardiovascular, Musculoskeletal, Skin and Neurological.
Measured: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Co-infections
To describe patient's Co-infections course during study.
Measured: 28 days
Results on patient´s Care Level
To describe patient´s care level course during study.
Measured: 28 days
Results on patient´s Mean arterial pressure(MAP)
To describe patient´s vital signs course during study by evaluating Mean arterial pressure(MAP)
Measured: 28 days
Results on patient´s heart rate (HR)
To describe patient´s vital signs course during study by evaluating heart rate (HR)
Measured: 28 days
Results on patient´s respiratory rate (RR)
To describe patient´s vital signs course during study by evaluating respiratory rate (RR)
Measured: 28 days
Results on patient´s 12-lead ECG
To describe patient´s 12-lead ECG result course during study.
Measured: day 0, 7, 14 and 28
Organ damage
To describe patient´s organ damage status during the study
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2020
- Study start15 Nov 2020
- Primary completion31 Aug 2021
- Study completion28 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for SARS-CoV 2Studies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is an open label pilot study involving 40 patients with COVID-19 disease. Patients that are hospitalized due to confirmed SARS-CoV-2 infection will be assigned to two groups according o their severity grade (moderate or severe).
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal College of Surgeons in Ireland - Medical University of Bahrain
- Sponsor type
- University, hospital or other
- Collaborators
- Bahrain Defence Force Hospital, Salmaniya Medical Complex
- Responsible party
- Sponsor
- Investigators
- Abdullah Darwish, Dr, Principal investigator, Bahrain Defense Force Royal Medical Services, Military Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04542850
- Sponsor's protocol ID
- 68 / 02-Aug-2020
- Status last verified
- Aug 2021
- First submitted
- 16 Aug 2020
- Last updated
- 9 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Monitoring, audits, and REC review will be permitted and provide direct access to source data and documents. The Lead PI and the researchers assigned by him will have access to the stored data/specimens. Only the Lead PI and the researchers assigned working on this study will be eligible to obtain the data/specimens from the participants during data collection.
Publications
El Kalamouni C, Frumence E, Bos S, Turpin J, Nativel B, Harrabi W, Wilkinson DA, Meilhac O, Gadea G, Despres P, Krejbich-Trotot P, Viranaicken W. Subversion of the Heme Oxygenase-1 Antiviral Activity by Zika Virus. Viruses. 2018 Dec 20;11(1):2. doi: 10.3390/v11010002.
PubMed 30577437Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580.
PubMed 1244564Devadas K, Dhawan S. Hemin activation ameliorates HIV-1 infection via heme oxygenase-1 induction. J Immunol. 2006 Apr 1;176(7):4252-7. doi: 10.4049/jimmunol.176.7.4252.
PubMed 16547262Hill-Batorski L, Halfmann P, Neumann G, Kawaoka Y. The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication. J Virol. 2013 Dec;87(24):13795-802. doi: 10.1128/JVI.02422-13. Epub 2013 Oct 9.
PubMed 24109237Hooper PL. COVID-19 and heme oxygenase: novel insight into the disease and potential therapies. Cell Stress Chaperones. 2020 Sep;25(5):707-710. doi: 10.1007/s12192-020-01126-9. Epub 2020 Jun 4.
PubMed 32500379Ibanez FJ, Farias MA, Retamal-Diaz A, Espinoza JA, Kalergis AM, Gonzalez PA. Pharmacological Induction of Heme Oxygenase-1 Impairs Nuclear Accumulation of Herpes Simplex Virus Capsids upon Infection. Front Microbiol. 2017 Oct 31;8:2108. doi: 10.3389/fmicb.2017.02108. eCollection 2017.
PubMed 29163402Ito H, Nishio Y, Hara T, Sugihara H, Tanaka T, Li XK. Oral administration of 5-aminolevulinic acid induces heme oxygenase-1 expression in peripheral blood mononuclear cells of healthy human subjects in combination with ferrous iron. Eur J Pharmacol. 2018 Aug 15;833:25-33. doi: 10.1016/j.ejphar.2018.05.009. Epub 2018 May 10.
PubMed 29753693Nishio Y, Fujino M, Zhao M, Ishii T, Ishizuka M, Ito H, Takahashi K, Abe F, Nakajima M, Tanaka T, Taketani S, Nagahara Y, Li XK. 5-Aminolevulinic acid combined with ferrous iron enhances the expression of heme oxygenase-1. Int Immunopharmacol. 2014 Apr;19(2):300-7. doi: 10.1016/j.intimp.2014.02.003. Epub 2014 Feb 13.
PubMed 24530569Ogawa K, Sun J, Taketani S, Nakajima O, Nishitani C, Sassa S, Hayashi N, Yamamoto M, Shibahara S, Fujita H, Igarashi K. Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1. EMBO J. 2001 Jun 1;20(11):2835-43. doi: 10.1093/emboj/20.11.2835.
PubMed 11387216Protzer U, Seyfried S, Quasdorff M, Sass G, Svorcova M, Webb D, Bohne F, Hosel M, Schirmacher P, Tiegs G. Antiviral activity and hepatoprotection by heme oxygenase-1 in hepatitis B virus infection. Gastroenterology. 2007 Oct;133(4):1156-65. doi: 10.1053/j.gastro.2007.07.021. Epub 2007 Jul 25.
PubMed 17919491Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev. 2006 Apr;86(2):583-650. doi: 10.1152/physrev.00011.2005.
PubMed 16601269Saito K, Fujiwara T, Ota U, Hatta S, Ichikawa S, Kobayashi M, Okitsu Y, Fukuhara N, Onishi Y, Ishizuka M, Tanaka T, Harigae H. Dynamics of absorption, metabolism, and excretion of 5-aminolevulinic acid in human intestinal Caco-2 cells. Biochem Biophys Rep. 2017 Jul 13;11:105-111. doi: 10.1016/j.bbrep.2017.07.006. eCollection 2017 Sep.
PubMed 28955775Schmidt WN, Mathahs MM, Zhu Z. Heme and HO-1 Inhibition of HCV, HBV, and HIV. Front Pharmacol. 2012 Oct 4;3:129. doi: 10.3389/fphar.2012.00129. eCollection 2012.
PubMed 23060790Tseng CK, Lin CK, Wu YH, Chen YH, Chen WC, Young KC, Lee JC. Human heme oxygenase 1 is a potential host cell factor against dengue virus replication. Sci Rep. 2016 Aug 24;6:32176. doi: 10.1038/srep32176.
PubMed 27553177Zhong M, Wang H, Ma L, Yan H, Wu S, Gu Z, Li Y. DMO-CAP inhibits influenza virus replication by activating heme oxygenase-1-mediated IFN response. Virol J. 2019 Feb 20;16(1):21. doi: 10.1186/s12985-019-1125-9.
PubMed 30786886
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Pilot Study to Evaluate the Safety, Tolerability, and Efficacy of 5-Aminolevulinic Acid Phosphate and Sodium Ferrous Citrate (5-ALA-Phosphate + SFC) in Subjects With SARS-CoV-2 Infection (COVID-19)
- ClinicalTrials.gov ID
- NCT04542850
- Acronym / sponsor ID
- 68 / 02-Aug-2020
- Conditions
- SARS-CoV 2, COVID-19
- Keywords
- 5-ALAPhosphate + SFC, COVID-19
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Royal College of Surgeons in Ireland - Medical University of BahrainUniversity, hospital or other
- Collaborators
- Bahrain Defence Force Hospital, Salmaniya Medical Complex
- Study start
- 15 Nov 2020 (actual)
- Primary completion
- 31 Aug 2021 (actual)
- Study completion
- 28 Oct 2021 (actual)
- First posted
- 9 Sep 2020 (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.
This is an open-label, interventional exploratory study to evaluate the safety and efficacy of 5-ALA-Phosphate + SFC in subjects with acute moderate or severe respiratory illness secondary to infection with SARS-CoV-2 virus (COVID-19) involving 40 subjects.
The primary objective is to evaluate the safety of 4-week oral administration of 5-ALAPhosphate + SFC. This study is expected to last for 4 weeks and will include follow-up until day 28 in the hospital or in an outpatient setting if the subjects are discharged earlier.
Detailed description
This is an open-label, interventional exploratory study to evaluate the safety and efficacy of 5-ALA-Phosphate + SFC in subjects with acute moderate or severe respiratory illness secondary to infection with SARS-CoV-2 virus (COVID-19).
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.
The primary endpoints of this study is- all treatment emergent AEs and SAEs Grade III and IV (CTC) with reasonable possibility of causal relationship to 5-ALA-Phosphate + SFC. 40 subjects with symptoms requiring hospitalization will be enrolled in thestudy, with 20 subjects enrolled in each group below:
Group 1: 20 Moderately ill hospitalized subjects not requiring assisted ventilation Group 2: 20 Severely ill hospitalized subjects requiring assisted ventilation
The duration of this clinical study will be 4 weeks, and follow-up will be performed until Day 28 in hospital, or in an outpatient setting if subjects improve and are discharged home or to alternative care facility.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is an open label pilot study involving 40 patients with COVID-19 disease. Patients that are hospitalized due to confirmed SARS-CoV-2 infection will be assigned to two groups according o their severity grade (moderate or severe).
| Arm | Type | Receives |
|---|---|---|
| Moderate group and Severe Group | Other | Dietary Supplement: 5-ALA-Phosphate + SFC (5-ALA + SFC)Moderate group and Severe group - . Both groups will be administered 5-aminolevulinic acid (5-ALA) is a natural delta amino acid widely present in nature that can be found in common food. 5-ALA combined with sodium ferrous citrate (SFC) produces the nutritional dietary supplement 5-ALA-Phosphate + SFC (5-ALA + SFC). |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Willing and able to provide written informed consent, or with a legal representative who can provide informed consent
- Aged ≥ 21 to 70 years
- Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test before beginning study dose regime
- qSOFA ≥ 1
- Currently hospitalized
Key exclusion criteria (13 listed)
- Subject has critical symptoms of COVID19 infection as defined as: high-flow oxygen therapy (>15 l/min delivered by nasal cannula or mask) or invasive mechanical ventilation signifying respiratory failure, septic shock, and/or multiple organ dysfunction ventilation at screening.
- Subject is nourished via a nasogastric tube
- 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
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 |
|---|---|---|
| 5-ALA-Phosphate + SFC (5-ALA + SFC)Moderately ill hospitalized patients will receive: 250 mg 5-ALA-Phosphate and 143.4 mg SFC (15.2 mg as Fe) two times daily (resulting in 500 mg 5-ALA-Phosphate and 286.8 mg SFC (30.4 mg as Fe) daily) for 7 days, then 250 mg 5-ALA-Phosphate and 143.4 mg SFC (15.2 mg as Fe) once daily for 21 days Severely ill hospitalized patients will receive: 250 mg 5-ALA-Phosphate and 143.4 mg SFC (15.2 mg as Fe) three times daily (resulting in 750 mg 5-ALA-Phosphate and 430.2 mg SFC (45.6 mg as Fe) daily) for 7 days, then 250 mg 5-ALA-Phosphate and 143.4 mg SFC (15.2 mg as Fe) once daily for 21 days | Dietary supplement | Moderate group and Severe Group |
Primary outcome
The incidence of treatment emergent Adverse Events (safety and tolerability) of 5-ALA-Phospate + SFC in patients with acute moderate or severe respiratory illness secondary to infection with SARS-CoV-2 virus (COVID-19).
Time frame: 28 days
To describe the incidence of treatment-emergent Adverse Events (TEAEs) of CTC Grades III and IV within four weeks following base line dose.
49 secondary outcomes
Sum COVID-19 Modified Ordinal Scale for Clinical Improvement maximum daily score over 28 days of dosing for Moderate group and for Severe group
Time frame: 28 days
Rate of change in COVID-19 Modified Ordinal Scale for Clinical Improvement maximum daily score over 28 days of dosing for individual subjects in Moderate group and in Severe group
Time frame: 28 days
Patient and subgroup profile of COVID-19 Modified Ordinal Scale for Clinical Improvement score vs. days hospitalized
Time frame: 28 days
Overall survival
Time frame: day 14 and day 28
Results of investigator´s assessment of patient´s oxygen therapy
Time frame: 28 days
Results of mechanical ventilation settings
Time frame: 28 days
Results of duration of ventilation
Time frame: from date of enrolment until the extubation or until last 5-ALA- Phosphate -SFC administration on day 28
The time to resolution of patient´s symptoms
Time frame: 28 days
Results of patient´s oxygen saturation (respiratory parameters)
Time frame: 28 days
Length of hospitalization
Time frame: From date of enrolment until last 5-ALA- Phosphate -SFC administration at day 28
The total time in ICU
Time frame: From date of enrolment until last 5-ALA- Phosphate -SFC administration at day 28
Results of investigator´s assessment of patient´s condition using (q)SOFA score
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s PT parameter
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s D-Dimer parameter
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s PTT parameter
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s SARS-CoV-2 viral load status (efficacy)
Time frame: day 7, 14 and 28
Results of patient´s Procalcitonin level.
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s IL-6 level
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s Serum Ferritin level
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s C-Reactive protein (CRP) level
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s T helper cells (CD4/CD8) level.
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results of patient´s Bilirubin level.
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Leucocytes
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Neutrophils
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Lymphocyte
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Platelets
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Hemoglobin
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Albumin
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s AST
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s ALT
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Total bilirubin
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Blood urea nitrogen
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Serum creatinine
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Creatinine kinase
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s LDH
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s Myoglobin glucose
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s aPTT
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s urine
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on hepatic function
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
Results on patient´s renal function
Time frame: day 0, 2, 3, 5, 7, 10, 14, 21, 28
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 9 Feb 2022.
- Background: PubMed 30577437El Kalamouni C, Frumence E, Bos S, Turpin J, Nativel B, Harrabi W, Wilkinson DA, Meilhac O, Gadea G, Despres P, Krejbich-Trotot P, Viranaicken W. Subversion of the Heme Oxygenase-1 Antiviral Activity by Zika Virus. Viruses. 2018 Dec 20;11(1):2. doi: 10.3390/v11010002.
- Background: PubMed 1244564Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580.
- Background: PubMed 16547262Devadas K, Dhawan S. Hemin activation ameliorates HIV-1 infection via heme oxygenase-1 induction. J Immunol. 2006 Apr 1;176(7):4252-7. doi: 10.4049/jimmunol.176.7.4252.
- Background: PubMed 24109237Hill-Batorski L, Halfmann P, Neumann G, Kawaoka Y. The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication. J Virol. 2013 Dec;87(24):13795-802. doi: 10.1128/JVI.02422-13. Epub 2013 Oct 9.
- Background: PubMed 32500379Hooper PL. COVID-19 and heme oxygenase: novel insight into the disease and potential therapies. Cell Stress Chaperones. 2020 Sep;25(5):707-710. doi: 10.1007/s12192-020-01126-9. Epub 2020 Jun 4.
- Background: PubMed 29163402Ibanez FJ, Farias MA, Retamal-Diaz A, Espinoza JA, Kalergis AM, Gonzalez PA. Pharmacological Induction of Heme Oxygenase-1 Impairs Nuclear Accumulation of Herpes Simplex Virus Capsids upon Infection. Front Microbiol. 2017 Oct 31;8:2108. doi: 10.3389/fmicb.2017.02108. eCollection 2017.
- Background: PubMed 29753693Ito H, Nishio Y, Hara T, Sugihara H, Tanaka T, Li XK. Oral administration of 5-aminolevulinic acid induces heme oxygenase-1 expression in peripheral blood mononuclear cells of healthy human subjects in combination with ferrous iron. Eur J Pharmacol. 2018 Aug 15;833:25-33. doi: 10.1016/j.ejphar.2018.05.009. Epub 2018 May 10.
- Background: PubMed 24530569Nishio Y, Fujino M, Zhao M, Ishii T, Ishizuka M, Ito H, Takahashi K, Abe F, Nakajima M, Tanaka T, Taketani S, Nagahara Y, Li XK. 5-Aminolevulinic acid combined with ferrous iron enhances the expression of heme oxygenase-1. Int Immunopharmacol. 2014 Apr;19(2):300-7. doi: 10.1016/j.intimp.2014.02.003. Epub 2014 Feb 13.
- Background: PubMed 11387216Ogawa K, Sun J, Taketani S, Nakajima O, Nishitani C, Sassa S, Hayashi N, Yamamoto M, Shibahara S, Fujita H, Igarashi K. Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1. EMBO J. 2001 Jun 1;20(11):2835-43. doi: 10.1093/emboj/20.11.2835.
- Background: PubMed 17919491Protzer U, Seyfried S, Quasdorff M, Sass G, Svorcova M, Webb D, Bohne F, Hosel M, Schirmacher P, Tiegs G. Antiviral activity and hepatoprotection by heme oxygenase-1 in hepatitis B virus infection. Gastroenterology. 2007 Oct;133(4):1156-65. doi: 10.1053/j.gastro.2007.07.021. Epub 2007 Jul 25.
- Background: PubMed 16601269Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev. 2006 Apr;86(2):583-650. doi: 10.1152/physrev.00011.2005.
- Background: PubMed 28955775Saito K, Fujiwara T, Ota U, Hatta S, Ichikawa S, Kobayashi M, Okitsu Y, Fukuhara N, Onishi Y, Ishizuka M, Tanaka T, Harigae H. Dynamics of absorption, metabolism, and excretion of 5-aminolevulinic acid in human intestinal Caco-2 cells. Biochem Biophys Rep. 2017 Jul 13;11:105-111. doi: 10.1016/j.bbrep.2017.07.006. eCollection 2017 Sep.
- Individual participant dataSharing planned: Yes. Monitoring, audits, and REC review will be permitted and provide direct access to source data and documents. The Lead PI and the researchers assigned by him will have access to the stored data/specimens. Only the Lead PI and the researchers assigned working on this study will be eligible to obtain the data/specimens from the participants during data collection.
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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.
Abdullah Darwish, Dr principal investigator
Bahrain Defense Force Royal Medical Services, Military Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 5-ALA-Phosphate + SFC (5-ALA + SFC) in people with SARS-CoV 2 and COVID-19, run by Royal College of Surgeons in Ireland - Medical University of Bahrain at 2 sites in Bahrain.
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 10 inclusion and 13 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 9 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Bahrain. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
The incidence of treatment emergent Adverse Events (safety and tolerability) of 5-ALA-Phospate + SFC in patients with acute moderate or severe respiratory illness secondary to infection with SARS-CoV-2 virus (COVID-19). (time frame: 28 days). 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 NCT04542850, which also lists 19 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 9 Feb 2022.