Inflammatory ResponsePhase 1/2NCT03772964
Effects of Metformin in a Non-Diabetic Patient Population
A Phase 1/2 study testing MetFORMIN Hydrochloride ER in people with Inflammatory Response, run by Brian Zuckerbraun at 1 site in United States.
Trial summary
Metformin has a well-established safety profile and it has become clear that metformin has additional salutary effects, including anti-inflammatory, anti-aging, and anti-thrombotic properties. Read more about this study
- Who is it for?
- Ages 55 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammatory Response
- What is being tested?
- MetFORMIN Hydrochloride ER
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jan 2019to 31 Mar 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age ≥55 and ≤85 years of age
- Non-diabetic
- Adjusted risk analysis index (RAI) 20-42
- Estimated glomerular filtration rate >45
- No evidence of hepatic dysfunction on comprehensive metabolic panel
- No clinical evidence of cardiac failure
- Existing University of Pittsburgh Medical Center Patients
Who cannot join
- Hypersensitivity to metformin or any component of the formulation
- Acute or chronic metabolic acidosis with or without coma
- Pregnant or breastfeeding females
- Evidence or history of hepatic, renal, or cardiopulmonary failure
- Excessive acute or chronic ethanol use
- Planned or known hospital admission, exposure to anesthesia, or surgical intervention 30 days prior to study or scheduled 30 days after the trial initiation
- Laboratory analysis showing HbgA1c >6.1 or eGFR <44 on baseline labs
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15209
About this study
Official title: A Pilot Study: Metformin as an Inflammatory Modulating Therapy in Older Adults Without Diabetes
Metformin has a well-established safety profile and it has become clear that metformin has additional salutary effects, including anti-inflammatory, anti-aging, and anti-thrombotic properties. In this study, subjects will provide both venous blood samples and stool samples in addition to completing cognitive and physiologic testing at baseline, throughout a 90 day exposure to metformin, and 30 days following exposure to metformin in order to evaluate their immune, microbiome, cellular respiration, thrombotic, and inflammatory responses.
Read the detailed description
Metformin is considered first-line therapy for patients with type two diabetes with hyperglycemia that cannot be controlled with lifestyle alone. Unlike other oral medications, metformin is favored for its insulin-sensitizing effects resulting in improved glycemic control, weight loss, and overall improvement of metabolic syndrome. Over the past fifteen years, metformin has received significant attention for its other potential therapeutic uses. Metformin has been found to decrease the rate of age-related illness progression improving longevity, especially in the setting of cancer. Recent clinical trials across multiple disease states have shown metformin to decrease all-cause mortality in diabetic and non-diabetic patients. Additionally, in both animal models and human trails, metformin has been shown to decrease the risk of arterial and venous thrombosis without affecting bleeding time through its interaction with platelet mitochondria. Although the mechanisms by which metformin effects longevity is an active area of both basic science and clinical research, it clearly has anti-inflammatory properties which are both independent and dependent of glycemic control. Recently, surgical outcomes have focused on optimizing older, deconditioned patients prior to the operation with varying protocols referred to as prehabilitation. These programs work to improve the body's response to the surgical stress resulting in improved wound healing, decreased postoperative complications, and decreased hospital length of stay. The affect of metformin, like increasing physical activity, has widespread affects on physiology. The investigators, therefore, hypothesize that metformin administration to non-diabetic adults will improve clinical outcomes to physiologic stress by improving underlying immune and inflammatory responses, that can be deleterious.
Subjects will have venous samples collected to better understand the cellular response to inflammation, thrombosis, and cellular respiration at baseline, at 4 time points throughout the 90 day exposure to metformin, and 30 days following the completion of exposure to metformin. At the same time points, subjects will have stool samples collected in order to assess changes in their microbiome. Finally, subjects will undergo cognitive testing through the NIH toolbox as well as physiologic testing including (six-minute walk test, grip strength as measured by a dynamometer, and a short physical performance battery) at baseline, after 90 days of exposure, and again 30 days after the completion of exposure.
- Conditions
- Inflammatory Response
- Being tested
- MetFORMIN Hydrochloride ER, Placebo
- Keywords
- prefrail, non-diabetic, metformin, thrombosis, microbiome, cellular respiration, short physical performance batter
- Medical subject headings
- Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetFORMIN Hydrochloride ERDrug
Also called Metformin ER
Subjects will be exposed to 500mg, 1000mg, or 1500mg of daily ER Metformin, by mouth, for up to 90 days. Subjects will have their venous blood sampled and baseline, throughout the trial, and following completion of their metformin exposure.
PlaceboDrug
Subjects will be exposed to placebo, by mouth, for up to 90 days. Subjects will have their venous blood sampled and baseline, throughout the trial, and following completion of their metformin exposure.
| Study group | Role | What they receive |
|---|---|---|
| 500mg exposure | Experimental | Subjects will be exposed to 500mg of daily MetFORMIN Hydrochloride ER for up to 90 days. Receives: Drug: MetFORMIN Hydrochloride ER |
| 1000mg exposure | Experimental | Subjects will be exposed to 1000mg of daily MetFORMIN Hydrochloride ER for up to 90 days. Receives: Drug: MetFORMIN Hydrochloride ER |
| 1500mg exposure | Experimental | Subjects will be exposed to 1500mg of daily MetFORMIN Hydrochloride ER for up to 90 days. Receives: Drug: MetFORMIN Hydrochloride ER |
| Placebo | Placebo comparator | Subjects will be exposed to placebo for up to 90 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ex Vivo Cytokine Response of Peripheral Blood Mononucleocytes (PBMC) to Inflammatory Stimuli Compared to Baseline, Throughout Exposure, and Following Exposure to Metformin.
Venous blood samples will be gathered throughout the study in order to quantify the changes in cytokine expression (FN-γ, IL-10, IL12p40, IL-12p70, IL-1α, IL1β, IL-2, IL-6, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, TNF-α) following ex vivo PBMC exposure to endotoxin.
Measured: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Secondary outcomes (8)
Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples.
Bacterial communities using 16S rRNA sequencing in relationship to metformin dosing over time. Species richness or diversity in the sample is measured by Choa1 metric. Chao1 is an estimate of how many species are present in an ecosystem. In general, having more species is considered to be "healthier" and these values typically range from 100-200 for fecal samples. The Chao1 index over numerous samples across time are explored to understand treatment effects.
Measured: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen.
Aggregometry area under the curve with the Y-axis being % aggregometry and the X-axis time in minutes.
Measured: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Measure the Rate of Thrombosis of Peripheral Blood.
The endpoints for isolated platelets include platelet activation as measured by FACS for CD62p.
Measured: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin.
The SPPB is a group of measures that combines the results of the gait speed, chair stand and balance tests. The minimum is zero (worse performance) and the maximum is 12 (best performance).
Measured: Day 0 (baseline), 90, and 120 (30 days post metformin exposure)
Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin.
Grip strength over time.
Measured: Day 0 (baseline), 90, and 120 (30 days post metformin exposure)
Mitochondrial Respiration in Both PBMCs and Platelets.
Oxidative phosphorylation, respiration, and complex activity will be tested using an Oroboros respirometer.
Measured: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Mitochondrial Content in Both PBMCs and Platelets.
Mitochondrial content will be measured by staining for mitotracker, and mitochondrial DNA oxidation will be determined by co-localizing staining for 8-hydroxydeoxyguanosine (8-OHdG). Markers of autophagy will be determined by measuring LC-3 flux, p62, beclin-1, and ATG7 protein levels.
Measured: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Measure Biogenesis of PBMCs.
Biogenesis will be determined by measuring RNA for PGC1a, NRF-1, and Tfam.
Measured: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2018
- Study start22 Jan 2019
- Primary completion31 Mar 2020
- Study completion31 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Inflammatory ResponseStudies 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 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will act as their own controls: data will be collect on each subject at baseline, throughout exposure and following, exposure to metformin.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brian Zuckerbraun
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Brian Zuckerbraun, University of Pittsburgh
- Investigators
- Brian Zuckerbraun, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03772964
- Sponsor's protocol ID
- PRO17100535
- Status last verified
- Dec 2022
- First submitted
- 28 Feb 2018
- Last updated
- 11 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is no current plan to make individual participant data available to other researchers.
Publications
Randriamboavonjy V, Mann WA, Elgheznawy A, Popp R, Rogowski P, Dornauf I, Drose S, Fleming I. Metformin reduces hyper-reactivity of platelets from patients with polycystic ovary syndrome by improving mitochondrial integrity. Thromb Haemost. 2015 Aug 31;114(3):569-78. doi: 10.1160/TH14-09-0797. Epub 2015 May 21.
PubMed 25993908Xin G, Wei Z, Ji C, Zheng H, Gu J, Ma L, Huang W, Morris-Natschke SL, Yeh JL, Zhang R, Qin C, Wen L, Xing Z, Cao Y, Xia Q, Lu Y, Li K, Niu H, Lee KH, Huang W. Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release. Sci Rep. 2016 Nov 2;6:36222. doi: 10.1038/srep36222.
PubMed 27805009Alazawi W, Pirmadjid N, Lahiri R, Bhattacharya S. Inflammatory and Immune Responses to Surgery and Their Clinical Impact. Ann Surg. 2016 Jul;264(1):73-80. doi: 10.1097/SLA.0000000000001691.
PubMed 27275778Kato M, Suzuki H, Murakami M, Akama M, Matsukawa S, Hashimoto Y. Elevated plasma levels of interleukin-6, interleukin-8, and granulocyte colony-stimulating factor during and after major abdominal surgery. J Clin Anesth. 1997 Jun;9(4):293-8. doi: 10.1016/s0952-8180(97)00006-8.
PubMed 9195352Lin E, Calvano SE, Lowry SF. Inflammatory cytokines and cell response in surgery. Surgery. 2000 Feb;127(2):117-26. doi: 10.1067/msy.2000.101584.
PubMed 10686974Jansson K, Redler B, Truedsson L, Magnuson A, Matthiessen P, Andersson M, Norgren L. Intraperitoneal cytokine response after major surgery: higher postoperative intraperitoneal versus systemic cytokine levels suggest the gastrointestinal tract as the major source of the postoperative inflammatory reaction. Am J Surg. 2004 Mar;187(3):372-7. doi: 10.1016/j.amjsurg.2003.12.019.
PubMed 15006565Whelan SP, Zuckerbraun BS. Mitochondrial signaling: forwards, backwards, and in between. Oxid Med Cell Longev. 2013;2013:351613. doi: 10.1155/2013/351613. Epub 2013 May 29.
PubMed 23819011Waltz P, Carchman EH, Young AC, Rao J, Rosengart MR, Kaczorowski D, Zuckerbraun BS. Lipopolysaccaride induces autophagic signaling in macrophages via a TLR4, heme oxygenase-1 dependent pathway. Autophagy. 2011 Mar;7(3):315-20. doi: 10.4161/auto.7.3.14044.
PubMed 21307647Keel M, Schregenberger N, Steckholzer U, Ungethum U, Kenney J, Trentz O, Ertel W. Endotoxin tolerance after severe injury and its regulatory mechanisms. J Trauma. 1996 Sep;41(3):430-7; discussion 437-8. doi: 10.1097/00005373-199609000-00008.
PubMed 8810959Loomba R, Lutchman G, Kleiner DE, Ricks M, Feld JJ, Borg BB, Modi A, Nagabhyru P, Sumner AE, Liang TJ, Hoofnagle JH. Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2009 Jan;29(2):172-82. doi: 10.1111/j.1365-2036.2008.03869.x. Epub 2008 Oct 9.
PubMed 18945255Hou X, Song J, Li XN, Zhang L, Wang X, Chen L, Shen YH. Metformin reduces intracellular reactive oxygen species levels by upregulating expression of the antioxidant thioredoxin via the AMPK-FOXO3 pathway. Biochem Biophys Res Commun. 2010 May 28;396(2):199-205. doi: 10.1016/j.bbrc.2010.04.017. Epub 2010 Apr 14.
PubMed 20398632Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009 Jul 16;460(7253):392-5. doi: 10.1038/nature08221. Epub 2009 Jul 8.
PubMed 19587680Algire C, Moiseeva O, Deschenes-Simard X, Amrein L, Petruccelli L, Birman E, Viollet B, Ferbeyre G, Pollak MN. Metformin reduces endogenous reactive oxygen species and associated DNA damage. Cancer Prev Res (Phila). 2012 Apr;5(4):536-43. doi: 10.1158/1940-6207.CAPR-11-0536. Epub 2012 Jan 18.
PubMed 22262811Smith DL Jr, Elam CF Jr, Mattison JA, Lane MA, Roth GS, Ingram DK, Allison DB. Metformin supplementation and life span in Fischer-344 rats. J Gerontol A Biol Sci Med Sci. 2010 May;65(5):468-74. doi: 10.1093/gerona/glq033. Epub 2010 Mar 19.
PubMed 20304770Pernicova I, Korbonits M. Metformin--mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol. 2014 Mar;10(3):143-56. doi: 10.1038/nrendo.2013.256. Epub 2014 Jan 7.
PubMed 24393785
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study: Metformin as an Inflammatory Modulating Therapy in Older Adults Without Diabetes
- ClinicalTrials.gov ID
- NCT03772964
- Acronym / sponsor ID
- PRO17100535
- Conditions
- Inflammatory Response
- Keywords
- prefrail, non-diabetic, metformin, thrombosis, microbiome, cellular respiration, short physical performance batter
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Brian ZuckerbraunUniversity, hospital or other
- Study start
- 22 Jan 2019 (actual)
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 31 Mar 2020 (actual)
- First posted
- 12 Dec 2018 (actual)
- Results
- Posted 11 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Metformin has a well-established safety profile and it has become clear that metformin has additional salutary effects, including anti-inflammatory, anti-aging, and anti-thrombotic properties. In this study, subjects will provide both venous blood samples and stool samples in addition to completing cognitive and physiologic testing at baseline, throughout a 90 day exposure to metformin, and 30 days following exposure to metformin in order to evaluate their immune, microbiome, cellular respiration, thrombotic, and inflammatory responses.
Detailed description
Metformin is considered first-line therapy for patients with type two diabetes with hyperglycemia that cannot be controlled with lifestyle alone. Unlike other oral medications, metformin is favored for its insulin-sensitizing effects resulting in improved glycemic control, weight loss, and overall improvement of metabolic syndrome. Over the past fifteen years, metformin has received significant attention for its other potential therapeutic uses. Metformin has been found to decrease the rate of age-related illness progression improving longevity, especially in the setting of cancer. Recent clinical trials across multiple disease states have shown metformin to decrease all-cause mortality in diabetic and non-diabetic patients. Additionally, in both animal models and human trails, metformin has been shown to decrease the risk of arterial and venous thrombosis without affecting bleeding time through its interaction with platelet mitochondria. Although the mechanisms by which metformin effects longevity is an active area of both basic science and clinical research, it clearly has anti-inflammatory properties which are both independent and dependent of glycemic control. Recently, surgical outcomes have focused on optimizing older, deconditioned patients prior to the operation with varying protocols referred to as prehabilitation. These programs work to improve the body's response to the surgical stress resulting in improved wound healing, decreased postoperative complications, and decreased hospital length of stay. The affect of metformin, like increasing physical activity, has widespread affects on physiology. The investigators, therefore, hypothesize that metformin administration to non-diabetic adults will improve clinical outcomes to physiologic stress by improving underlying immune and inflammatory responses, that can be deleterious.
Subjects will have venous samples collected to better understand the cellular response to inflammation, thrombosis, and cellular respiration at baseline, at 4 time points throughout the 90 day exposure to metformin, and 30 days following the completion of exposure to metformin. At the same time points, subjects will have stool samples collected in order to assess changes in their microbiome. Finally, subjects will undergo cognitive testing through the NIH toolbox as well as physiologic testing including (six-minute walk test, grip strength as measured by a dynamometer, and a short physical performance battery) at baseline, after 90 days of exposure, and again 30 days after the completion of exposure.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- Model description
- Subjects will act as their own controls: data will be collect on each subject at baseline, throughout exposure and following, exposure to metformin.
| Arm | Type | Receives |
|---|---|---|
| 500mg exposure | Experimental | Drug: MetFORMIN Hydrochloride ERSubjects will be exposed to 500mg of daily MetFORMIN Hydrochloride ER for up to 90 days. |
| 1000mg exposure | Experimental | Drug: MetFORMIN Hydrochloride ERSubjects will be exposed to 1000mg of daily MetFORMIN Hydrochloride ER for up to 90 days. |
| 1500mg exposure | Experimental | Drug: MetFORMIN Hydrochloride ERSubjects will be exposed to 1500mg of daily MetFORMIN Hydrochloride ER for up to 90 days. |
| Placebo | Placebo comparator | Drug: PlaceboSubjects will be exposed to placebo for up to 90 days. |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥55 and ≤85 years of age
- Non-diabetic
- Adjusted risk analysis index (RAI) 20-42
- Estimated glomerular filtration rate >45
- No evidence of hepatic dysfunction on comprehensive metabolic panel
Key exclusion criteria (7 listed)
- Hypersensitivity to metformin or any component of the formulation
- Acute or chronic metabolic acidosis with or without coma
- Pregnant or breastfeeding females
- Evidence or history of hepatic, renal, or cardiopulmonary failure
- Excessive acute or chronic ethanol use
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 |
|---|---|---|
| MetFORMIN Hydrochloride ERAlso: Metformin ERSubjects will be exposed to 500mg, 1000mg, or 1500mg of daily ER Metformin, by mouth, for up to 90 days. Subjects will have their venous blood sampled and baseline, throughout the trial, and following completion of their metformin exposure. | Drug | 1000mg exposure, 1500mg exposure, 500mg exposure |
| PlaceboSubjects will be exposed to placebo, by mouth, for up to 90 days. Subjects will have their venous blood sampled and baseline, throughout the trial, and following completion of their metformin exposure. | Drug | Placebo |
Primary outcome
Ex Vivo Cytokine Response of Peripheral Blood Mononucleocytes (PBMC) to Inflammatory Stimuli Compared to Baseline, Throughout Exposure, and Following Exposure to Metformin.
Time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Venous blood samples will be gathered throughout the study in order to quantify the changes in cytokine expression (FN-γ, IL-10, IL12p40, IL-12p70, IL-1α, IL1β, IL-2, IL-6, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, TNF-α) following ex vivo PBMC exposure to endotoxin.
8 secondary outcomes
Quantify the Bacterial Population Profile of the Microbiome Via Stool Samples.
Time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Measure the Rate of Clotting of Peripheral Blood With Whole Blood Aggregometry in Response to Collagen.
Time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Measure the Rate of Thrombosis of Peripheral Blood.
Time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Changes From Baseline in Short Physical Performance Battery (SPPB) During and Following Exposure to Metformin.
Time frame: Day 0 (baseline), 90, and 120 (30 days post metformin exposure)
Changes From Baseline in Grip Strength Via a Dynamometer During and Following Exposure to Metformin.
Time frame: Day 0 (baseline), 90, and 120 (30 days post metformin exposure)
Mitochondrial Respiration in Both PBMCs and Platelets.
Time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Mitochondrial Content in Both PBMCs and Platelets.
Time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Measure Biogenesis of PBMCs.
Time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25993908Randriamboavonjy V, Mann WA, Elgheznawy A, Popp R, Rogowski P, Dornauf I, Drose S, Fleming I. Metformin reduces hyper-reactivity of platelets from patients with polycystic ovary syndrome by improving mitochondrial integrity. Thromb Haemost. 2015 Aug 31;114(3):569-78. doi: 10.1160/TH14-09-0797. Epub 2015 May 21.
- Background: PubMed 27805009Xin G, Wei Z, Ji C, Zheng H, Gu J, Ma L, Huang W, Morris-Natschke SL, Yeh JL, Zhang R, Qin C, Wen L, Xing Z, Cao Y, Xia Q, Lu Y, Li K, Niu H, Lee KH, Huang W. Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release. Sci Rep. 2016 Nov 2;6:36222. doi: 10.1038/srep36222.
- Background: PubMed 27275778Alazawi W, Pirmadjid N, Lahiri R, Bhattacharya S. Inflammatory and Immune Responses to Surgery and Their Clinical Impact. Ann Surg. 2016 Jul;264(1):73-80. doi: 10.1097/SLA.0000000000001691.
- Background: PubMed 9195352Kato M, Suzuki H, Murakami M, Akama M, Matsukawa S, Hashimoto Y. Elevated plasma levels of interleukin-6, interleukin-8, and granulocyte colony-stimulating factor during and after major abdominal surgery. J Clin Anesth. 1997 Jun;9(4):293-8. doi: 10.1016/s0952-8180(97)00006-8.
- Background: PubMed 10686974Lin E, Calvano SE, Lowry SF. Inflammatory cytokines and cell response in surgery. Surgery. 2000 Feb;127(2):117-26. doi: 10.1067/msy.2000.101584.
- Background: PubMed 15006565Jansson K, Redler B, Truedsson L, Magnuson A, Matthiessen P, Andersson M, Norgren L. Intraperitoneal cytokine response after major surgery: higher postoperative intraperitoneal versus systemic cytokine levels suggest the gastrointestinal tract as the major source of the postoperative inflammatory reaction. Am J Surg. 2004 Mar;187(3):372-7. doi: 10.1016/j.amjsurg.2003.12.019.
- Background: PubMed 23819011Whelan SP, Zuckerbraun BS. Mitochondrial signaling: forwards, backwards, and in between. Oxid Med Cell Longev. 2013;2013:351613. doi: 10.1155/2013/351613. Epub 2013 May 29.
- Background: PubMed 21307647Waltz P, Carchman EH, Young AC, Rao J, Rosengart MR, Kaczorowski D, Zuckerbraun BS. Lipopolysaccaride induces autophagic signaling in macrophages via a TLR4, heme oxygenase-1 dependent pathway. Autophagy. 2011 Mar;7(3):315-20. doi: 10.4161/auto.7.3.14044.
- Background: PubMed 8810959Keel M, Schregenberger N, Steckholzer U, Ungethum U, Kenney J, Trentz O, Ertel W. Endotoxin tolerance after severe injury and its regulatory mechanisms. J Trauma. 1996 Sep;41(3):430-7; discussion 437-8. doi: 10.1097/00005373-199609000-00008.
- Background: PubMed 18945255Loomba R, Lutchman G, Kleiner DE, Ricks M, Feld JJ, Borg BB, Modi A, Nagabhyru P, Sumner AE, Liang TJ, Hoofnagle JH. Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2009 Jan;29(2):172-82. doi: 10.1111/j.1365-2036.2008.03869.x. Epub 2008 Oct 9.
- Background: PubMed 20398632Hou X, Song J, Li XN, Zhang L, Wang X, Chen L, Shen YH. Metformin reduces intracellular reactive oxygen species levels by upregulating expression of the antioxidant thioredoxin via the AMPK-FOXO3 pathway. Biochem Biophys Res Commun. 2010 May 28;396(2):199-205. doi: 10.1016/j.bbrc.2010.04.017. Epub 2010 Apr 14.
- Background: PubMed 19587680Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009 Jul 16;460(7253):392-5. doi: 10.1038/nature08221. Epub 2009 Jul 8.
- Individual participant dataSharing planned: No. There is no current plan to make individual participant data available to other researchers.
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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.
Brian Zuckerbraun, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MetFORMIN Hydrochloride ER in people with Inflammatory Response, run by Brian Zuckerbraun at 1 site in United States.
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 7 inclusion and 7 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 11 Jan 2023. 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 United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Ex Vivo Cytokine Response of Peripheral Blood Mononucleocytes (PBMC) to Inflammatory Stimuli Compared to Baseline, Throughout Exposure, and Following Exposure to Metformin. (time frame: Day 0 (baseline), 30, 60, 90, and 120 (30 days post metformin exposure)). 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 NCT03772964, which also lists 15 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 11 Jan 2023.