Iron-deficiencypolySICNCT04849832
Effect of Polyphenols on Absorption of Iron From Sodium Iron Chlorophyllin
A study testing SIC, SIC + tea and FeSO4 in people with Iron-deficiency, run by Swiss Federal Institute of Technology at 1 site in Switzerland.
Trial summary
Polyphenols present in tea are known to inhibit the absorption of non heme iron. The inhibiting effect of tea on non-heme iron absorption is attributed to the flavonoids present in tea. It is well known that Ferrous sulfate is not absorbed well in the presence of polyphenols. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Iron-deficiency
- What is being tested?
- SIC, SIC + tea and FeSO4
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteSwitzerland
- Study dates
- 21 Jun 2021to 26 Jul 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 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- female aged between 18-45 y old;
- SF <80 µg/L;
- BMI 18.5-24.9 kg/m2;
- weight <70 kg;
- signed informed consent;
- able to communicate and comprehend English language.
Who cannot join
- anemia (Hb <12 g/dL);
- Inflammation (CRP > 5 mg/L);
- chronic digestive, renal and/or metabolic disease;
- chronic medications (except for oral contraceptives);
- use of vitamin, mineral and pre- and/or probiotic supplements in the previous 2 weeks before study initiation and during the course of the study;
- blood transfusion, blood donation or significant blood loss over the past 4 months;
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- difficulties with blood sampling;
- antibiotic treatment in the 4 weeks before study initiation;
- pregnancy (tested in serum at screening) or intention to become pregnant;
- lactation up to 6 weeks before study initiation;
- earlier participation in a study using stable isotopes or participation in any clinical study within the last 30 days;
- unable to comply with study protocol (e.g. not available on certain study appointment days or difficulties with blood withdrawal);
- inability to understand the information sheet and the informed consent form due to cognitive or language reasons;
- smoking;
- unwilling to use an effective method of contraception.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
ETH Zürich, Laboratory of Human Nutrition
Zurich, Canton of Zurich, 8092
About this study
Official title: Evaluating the Effect of Polyphenols on the Iron Bioavailability From Iron Chlorophyllin in Young Women Using the Iron Stable Isotopic Method
Polyphenols present in tea are known to inhibit the absorption of non heme iron. The inhibiting effect of tea on non-heme iron absorption is attributed to the flavonoids present in tea. It is well known that Ferrous sulfate is not absorbed well in the presence of polyphenols. We would like to evaluate the effect of polyphenols on the newly developed compound, sodium iron chlorophyllin (SIC), which mimics the heme iron structure. Comparisons of fractional absorption of SIC and Ferrous Sulfate in the presence of polyphenols can help identify the performance of the compounds as vehicles for iron delivery in the presence of iron absorption inhibitors.
In a single-blind randomized cross-over study using stable iron isotope technique, iron bioavailability from SIC delivered with an inhibitory matrix can therefore be determined when given along with black tea
Read the detailed description
New approaches to treat iron deficiency include developing novel iron compounds with possible iron absorption routes that increase iron bioavailability and reduce gastrointestinal side effects.
Sodium iron chlorophyllin (SIC) is a water-soluble semisynthetic chlorophyll derivative where the magnesium in the porphyrin ring has been substituted by iron. Given the porphyrin ring heme-like structure of SIC, it may be an alternative delivery route for iron, suitable also for vegetarians and vegans. Yet, there are few studies investigating the use of SIC for this purpose.
We recently completed the study entitled "Evaluation of iron bioavailability from iron chlorophyllin in young women using the iron stable isotopic method" based on previous in vitro and in vivo studies.. The study showed a 7% fractional iron absorption (FIA) from SIC when compared to the control compound, ferrous sulfate, which had a FIA of 30%, indicating a Relative Bioavailability of SIC of 20%. The study showed an inverse relationship between ferritin status and iron absorption from SIC in the study participants and an increase in the FIA in the presence of ascorbic acid. Both these findings lean towards the possibility that that the iron contributing to the FIA from SIC may be iron that was dissociated from the porphyrin ring of the chlorophyllin and entering the common non heme iron pool. This inverse relationship in ferritin and FIA is well known for ferrous sulfate. However, one cannot confirm the pathway taken up by SIC to deliver iron based on the previous study alone.
Polyphenols present in tea are known to inhibit the absorption of non heme iron.The inhibiting effect of tea on non-heme iron absorption is attributed to the flavonoids present in tea. There are several types of tea flavonoids: monomers (catechin), dimers (theaflavin), and polymers (thearubigin). Black tea contains 10% flavanols, 25% catechins, 20% theaflavins and 45% thearubigins. The mechanism of iron absorption inhibition by tea is by formation of a complex of the flavonoids with iron. It is mainly the galloyl group in these phenolic compounds that specifically binds iron. A cup of black tea, brewed with 2.5 g tea leaves contains about 200 mg tea flavonoids . Heme iron absorption has also been shown to be inhibited by the presence of polyphenols but unclear to what extent. Thus, comparisons of fractional absorption of SIC and Ferrous Sulfate in the presence of polyphenols can help identify the performance of the compounds as vehicles for iron delivery in the presence of iron absorption inhibitors.
In a single-blind randomized cross-over study using stable iron isotope technique, iron bioavailability from SIC delivered with an inhibitory matrix can therefore be determined when given along with black tea.
SIC has been produced at the HNL with a 50% incorporation of iron into the chlorophyll. Our protocol is based on a Unilever patent that is no longer active, with in-house adaptation. The SIC has a neutral taste and will be presented as a dark green liquid, being the solution of SIC in water.
If SIC, as hypothesized, behaves in a similar way to heme, then iron absorption inhibitors, such as the polyphenols, will not have an effect on the absorption of iron from SIC.
- Conditions
- Iron-deficiency
- Being tested
- SIC, SIC + tea, FeSO4, FeSO4 + tea
- Medical subject headings
- Anemia, Iron-Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SICDietary supplement
Sodium Iron Chlorophyllin as prepared by the human nutrition laboratory, ETH Zurich
SIC + teaDietary supplement
Sodium Iron Chlorophyllin as prepared by the human nutrition laboratory, ETH Zurich with 2g of tea brewed for 5 minutes
FeSO4Dietary supplement
Ferrous sulfate solution serves as a positive control - and whose absorption is well known.
FeSO4 + teaDietary supplement
Ferrous sulfate solution given with 2g of tea brewed for 5 minutes - expected iron absorption inhibition
| Study group | Role | What they receive |
|---|---|---|
| SIC | Experimental | 4mg of Fe will be given as 102 mg of SIC as a solution Receives: Dietary Supplement: SIC |
| SIC + tea | Experimental | 4 mg of Fe will be given as 102 mg of SIC as a solution along with 200 ml of black tea Receives: Dietary Supplement: SIC + tea |
| FeSO4 | Active comparator | 4 mg of Fe will be given as Ferrous sulfate solution Receives: Dietary Supplement: FeSO4 |
| FeSO4 + tea | Active comparator | 4 mg of Fe will be given as Ferrous sulfate solution along with 200 ml of black tea Receives: Dietary Supplement: FeSO4 + tea |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio of FIA of SIC arms vs ratio of FIA of Ferrous sulfate arms
ratio of iron bioavailability (as measured by erythrocyte incorporation of the stable isotope labels) from SIC in a polyphenol matrix to that from SIC alone with the ratio of iron bioavailability from FeSO4 in a polyphenol matrix to that from FeSO4 alone.
Measured: Day 1 of the study
Ratio of FIA of SIC arms vs ratio of FIA of Ferrous sulfate arms
ratio of iron bioavailability (as measured by erythrocyte incorporation of the stable isotope labels) from SIC in a polyphenol matrix to that from SIC alone with the ratio of iron bioavailability from FeSO4 in a polyphenol matrix to that from FeSO4 alone.
Measured: Day 17 of the study
Ratio of FIA of SIC arms vs ratio of FIA of Ferrous sulfate arms
ratio of iron bioavailability (as measured by erythrocyte incorporation of the stable isotope labels) from SIC in a polyphenol matrix to that from SIC alone with the ratio of iron bioavailability from FeSO4 in a polyphenol matrix to that from FeSO4 alone.
Measured: Day 33 of the study
Secondary outcomes (4)
Hemoglobin
Iron status biomarker
Measured: day 1, day 17 and day 33 of the the study
Ferritin
Iron status biomarker
Measured: day 1, day 17 and day 33 of the the study
sTfR
Iron status biomarker
Measured: day 1, day 17 and day 33 of the the study
C-reactive Protein
Inflammation marker
Measured: day 1, day 17 and day 33 of the the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2021
- Study start21 Jun 2021
- Primary completion26 Jul 2021
- Study completion26 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Iron-deficiencyStudies 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
- Randomised
- Intervention model
- Crossover
- Model description
- The study will be a randomized, single centre cross over study where every participant will receive all the four interventions.
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swiss Federal Institute of Technology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jessica Farebrother, Dr.Sc, Principal investigator, ETH Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04849832
- Sponsor's protocol ID
- PolySIC
- Acronym
- polySIC
- Status last verified
- Nov 2021
- First submitted
- 15 Apr 2021
- Last updated
- 26 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Effect of Polyphenols on the Iron Bioavailability From Iron Chlorophyllin in Young Women Using the Iron Stable Isotopic Method
- ClinicalTrials.gov ID
- NCT04849832
- Acronym / sponsor ID
- polySIC / PolySIC
- Conditions
- Iron-deficiency
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Swiss Federal Institute of TechnologyUniversity, hospital or other
- Study start
- 21 Jun 2021 (actual)
- Primary completion
- 26 Jul 2021 (actual)
- Study completion
- 26 Jul 2021 (actual)
- First posted
- 19 Apr 2021 (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.
Polyphenols present in tea are known to inhibit the absorption of non heme iron. The inhibiting effect of tea on non-heme iron absorption is attributed to the flavonoids present in tea. It is well known that Ferrous sulfate is not absorbed well in the presence of polyphenols. We would like to evaluate the effect of polyphenols on the newly developed compound, sodium iron chlorophyllin (SIC), which mimics the heme iron structure. Comparisons of fractional absorption of SIC and Ferrous Sulfate in the presence of polyphenols can help identify the performance of the compounds as vehicles for iron delivery in the presence of iron absorption inhibitors.
In a single-blind randomized cross-over study using stable iron isotope technique, iron bioavailability from SIC delivered with an inhibitory matrix can therefore be determined when given along with black tea
Detailed description
New approaches to treat iron deficiency include developing novel iron compounds with possible iron absorption routes that increase iron bioavailability and reduce gastrointestinal side effects.
Sodium iron chlorophyllin (SIC) is a water-soluble semisynthetic chlorophyll derivative where the magnesium in the porphyrin ring has been substituted by iron. Given the porphyrin ring heme-like structure of SIC, it may be an alternative delivery route for iron, suitable also for vegetarians and vegans. Yet, there are few studies investigating the use of SIC for this purpose.
We recently completed the study entitled "Evaluation of iron bioavailability from iron chlorophyllin in young women using the iron stable isotopic method" based on previous in vitro and in vivo studies.. The study showed a 7% fractional iron absorption (FIA) from SIC when compared to the control compound, ferrous sulfate, which had a FIA of 30%, indicating a Relative Bioavailability of SIC of 20%. The study showed an inverse relationship between ferritin status and iron absorption from SIC in the study participants and an increase in the FIA in the presence of ascorbic acid. Both these findings lean towards the possibility that that the iron contributing to the FIA from SIC may be iron that was dissociated from the porphyrin ring of the chlorophyllin and entering the common non heme iron pool. This inverse relationship in ferritin and FIA is well known for ferrous sulfate. However, one cannot confirm the pathway taken up by SIC to deliver iron based on the previous study alone.
Polyphenols present in tea are known to inhibit the absorption of non heme iron.The inhibiting effect of tea on non-heme iron absorption is attributed to the flavonoids present in tea. There are several types of tea flavonoids: monomers (catechin), dimers (theaflavin), and polymers (thearubigin). Black tea contains 10% flavanols, 25% catechins, 20% theaflavins and 45% thearubigins. The mechanism of iron absorption inhibition by tea is by formation of a complex of the flavonoids with iron. It is mainly the galloyl group in these phenolic compounds that specifically binds iron. A cup of black tea, brewed with 2.5 g tea leaves contains about 200 mg tea flavonoids . Heme iron absorption has also been shown to be inhibited by the presence of polyphenols but unclear to what extent. Thus, comparisons of fractional absorption of SIC and Ferrous Sulfate in the presence of polyphenols can help identify the performance of the compounds as vehicles for iron delivery in the presence of iron absorption inhibitors.
In a single-blind randomized cross-over study using stable iron isotope technique, iron bioavailability from SIC delivered with an inhibitory matrix can therefore be determined when given along with black tea.
SIC has been produced at the HNL with a 50% incorporation of iron into the chlorophyll. Our protocol is based on a Unilever patent that is no longer active, with in-house adaptation. The SIC has a neutral taste and will be presented as a dark green liquid, being the solution of SIC in water.
If SIC, as hypothesized, behaves in a similar way to heme, then iron absorption inhibitors, such as the polyphenols, will not have an effect on the absorption of iron from SIC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- The study will be a randomized, single centre cross over study where every participant will receive all the four interventions.
| Arm | Type | Receives |
|---|---|---|
| SIC | Experimental | Dietary Supplement: SIC4mg of Fe will be given as 102 mg of SIC as a solution |
| SIC + tea | Experimental | Dietary Supplement: SIC + tea4 mg of Fe will be given as 102 mg of SIC as a solution along with 200 ml of black tea |
| FeSO4 | Active comparator | Dietary Supplement: FeSO44 mg of Fe will be given as Ferrous sulfate solution |
| FeSO4 + tea | Active comparator | Dietary Supplement: FeSO4 + tea4 mg of Fe will be given as Ferrous sulfate solution along with 200 ml of black tea |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- female aged between 18-45 y old;
- SF <80 µg/L;
- BMI 18.5-24.9 kg/m2;
- weight <70 kg;
- signed informed consent;
Key exclusion criteria (15 listed)
- anemia (Hb <12 g/dL);
- Inflammation (CRP > 5 mg/L);
- chronic digestive, renal and/or metabolic disease;
- chronic medications (except for oral contraceptives);
- use of vitamin, mineral and pre- and/or probiotic supplements in the previous 2 weeks before study initiation and during the course of the study;
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 |
|---|---|---|
| SICSodium Iron Chlorophyllin as prepared by the human nutrition laboratory, ETH Zurich | Dietary supplement | SIC |
| SIC + teaSodium Iron Chlorophyllin as prepared by the human nutrition laboratory, ETH Zurich with 2g of tea brewed for 5 minutes | Dietary supplement | SIC + tea |
| FeSO4Ferrous sulfate solution serves as a positive control - and whose absorption is well known. | Dietary supplement | FeSO4 |
| FeSO4 + teaFerrous sulfate solution given with 2g of tea brewed for 5 minutes - expected iron absorption inhibition | Dietary supplement | FeSO4 + tea |
Primary outcome
Ratio of FIA of SIC arms vs ratio of FIA of Ferrous sulfate arms
Time frame: Day 1 of the study
ratio of iron bioavailability (as measured by erythrocyte incorporation of the stable isotope labels) from SIC in a polyphenol matrix to that from SIC alone with the ratio of iron bioavailability from FeSO4 in a polyphenol matrix to that from FeSO4 alone.
Ratio of FIA of SIC arms vs ratio of FIA of Ferrous sulfate arms
Time frame: Day 17 of the study
ratio of iron bioavailability (as measured by erythrocyte incorporation of the stable isotope labels) from SIC in a polyphenol matrix to that from SIC alone with the ratio of iron bioavailability from FeSO4 in a polyphenol matrix to that from FeSO4 alone.
Ratio of FIA of SIC arms vs ratio of FIA of Ferrous sulfate arms
Time frame: Day 33 of the study
ratio of iron bioavailability (as measured by erythrocyte incorporation of the stable isotope labels) from SIC in a polyphenol matrix to that from SIC alone with the ratio of iron bioavailability from FeSO4 in a polyphenol matrix to that from FeSO4 alone.
4 secondary outcomes
Hemoglobin
Time frame: day 1, day 17 and day 33 of the the study
Ferritin
Time frame: day 1, day 17 and day 33 of the the study
sTfR
Time frame: day 1, day 17 and day 33 of the the study
C-reactive Protein
Time frame: day 1, day 17 and day 33 of the the study
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 26 Nov 2021.
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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.
Jessica Farebrother, Dr.Sc principal investigator
ETH Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SIC, SIC + tea and FeSO4 in people with Iron-deficiency, run by Swiss Federal Institute of Technology at 1 site in Switzerland.
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 6 inclusion and 15 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 26 Nov 2021. 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 Switzerland. 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?
Ratio of FIA of SIC arms vs ratio of FIA of Ferrous sulfate arms (time frame: Day 1 of the study). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Nov 2021.