Atherosclerosis of ArteryPhase 1RENEWALNCT05908513
NAC Treatment and Outcomes in Patients With Advanced Atherosclerosis and DM
A Phase 1 study testing N-acetylcysteine in people with Atherosclerosis of Artery and Peripheral Artery Disease, run by University of Missouri-Columbia at 2 sites in China.
Trial summary
Atherosclerosis and diabetes are related to coronary artery disease and peripheral artery disease. The mechanisms are related to increased reactive oxygen species (ROS) formation and inflammatory cytokine secretion. However, simply using antioxidant or anti-inflammatory therapies has no optimal outcomes. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Atherosclerosis of Artery, Peripheral Artery Disease, Diabetes Mellitus
- What is being tested?
- N-acetylcysteine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 2 sitesChina
- Study dates
- 15 Oct 2021to 15 Oct 2021
- Phase
- Phase 1
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1) significant coronary artery disease (CAD) and not a candidate for revascularization (CABG or PCI), or 2) significant peripheral artery disease (PAD) with or without critical limb ischemia (CLI) or chronic ulcers.
Who cannot join
- 1) Pregnant or nursing (lactating) women, confirmed by a positive hCG laboratory test 2). Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are a. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone or partial or total hysterectomy, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
- 3). Planned coronary revascularization (PCI or CABG) or any other major surgical procedure.
- 4). Major non-cardiac surgical or major endoscopic procedure within the past 6 months prior to the initial visit (Visit 1) 5). Multi-vessel CABG surgery within the past 3 years 6). Symptomatic patients with Class IV heart failure (HF) (New York Heart Association).
- 7). Uncontrolled hypertension (defined as an average SBP >180 mmHg or an average diastolic blood pressure (DBP) >110 mmHg at Visit 1. Patients are allowed to be re-evaluated, at the discretion of investigator for this criterion if anti-hypertensive therapy has been started or increased as a result of initial screening blood pressure above these limits.
- 8). Uncontrolled diabetes with persistent fasting blood glucose level of 300 or A1C of 7.5 for 3 months or defined by the investigator 9). Kidney or other organ transplant (due to anti-immune therapy) at Visit 1 10). Prior malignancy other than basal cell skin carcinoma. 11). A history of alcohol and/or substance abuse that could interfere with the conduct of the trial.
- 12). History of ongoing, chronic or recurrent infectious disease except hepatitis.
- 13). History of hypersensitivity to NAC. 14). Patients who have received an investigational drug or device within 30 days (inclusive) of Visit 1, or who are expected to participate in any other investigational drug or device study during the conduct of this trial, except for patients who have an investigational drug eluting stent (DES), provided that they have completed the DES trial. FDA/country-specific drug regulatory authority approved DES devices are permitted.
- 15). Any life threatening condition with life expectancy < 3 years, other than vascular disease that might prevent the patient from completing the study.
Trial locations and contacts
2 sites in 1 country.
China2 sites
The Second Xiangya Hospital of Central South University
Changsha, Hunan, 410011
Shandong Provincial Hospital
Jinan, Shandong, 250021
About this study
Official title: Randomized Study on N-acetylcysteine Treatment and Outcomes in Patients With Advanced Atherosclerotic Heart Diseases and Diabetes Mellitus (RENEWAL)
Atherosclerosis and diabetes are related to coronary artery disease and peripheral artery disease. The mechanisms are related to increased reactive oxygen species (ROS) formation and inflammatory cytokine secretion. However, simply using antioxidant or anti-inflammatory therapies has no optimal outcomes. On the other hand, N-acetylcysteine (NAC) which has both antioxidant and anti-inflammatory effects could effectively attenuate ROS production and reduce vascular inflammation. Hence, we will investigate the effect of NAC treatment on the outcomes in patients with advanced atherosclerotic heart diseases and patients with diabetes combined with significant peripheral artery disease.
Read the detailed description
Atherosclerosis is a chronic inflammatory disease and remains one of the major causes of death globally, despite aggressive risk stratifications including smoking cessation, optimal control of lipid, blood pressure, and diabetes. Antioxidant therapies with vitamin E and C or β-carotene failed to achieve significant clinical benefits in patients with cardiovascular diseases (CVD) including atherosclerosis. New therapies including interleukin-1β monoclonal antibody canakinumab and anti-inflammatory drug colchicine could significantly reduce the rate of major adverse cardiovascular events (MACE) including nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. However, canakinumab therapy did not decrease all-cause mortality, and was associated with a significant increase in the incidence of fatal infection (including sepsis), and high cost. While colchicine is a generic drug and decreases the rate of MACE, colchicine therapy is associated with a significant increase in death from non-cardiovascular causes5. Thus, alternative options are needed to attenuate atherosclerosis. N-acetylcysteine (NAC) has been traditionally considered an antioxidant although it is more like an anti-inflammatory agent, and could effectively attenuate reactive oxygen species (ROS) production, and reduce vascular inflammation. NAC significantly decreases the progression of atherosclerosis in young apolipoprotein E-deficient mice and low-density lipoprotein receptor deficient (LDLR-/-) mice with an atherogenic high fat diet (HFD). NAC treatment delays cellular senescence in endothelial cells from atherosclerotic patients, and improves coronary and peripheral endothelium-dependent vasodilation in human subjects with or without atherosclerosis. NAC treatment also inhibits oxidized LDL-induced foam cell formation and suppresses matrix-degrading capacity of foam cells. However, it is unclear if NAC could attenuate the progression of atherosclerosis or reverse the course of atherosclerosis in aging mice. Diabetes mellitus (DM) significantly increases the risk of developing severe peripheral artery disease (PAD) with critical limb ischemia (CLI) and chronic ulcers. Due to poor healing, patients with diabetic CLI may need limb amputation that accounts for about 60% of all non-traumatic amputations in the U. S. After a two decade reduction in diabetes-related non-traumatic lower-extremity amputation, recent data show an increase in amputation, particularly in young and middle-aged adults. In addition, major randomized clinical trials have shown that blood glucose-lowering or anti-hypertensive therapies have very limited effects on reducing macrovascular complications, and no benefit on amputation rates in diabetic patients. These highlight an urgent need for alterative effective approaches to promoting the recovery of diabetic ischemic limb to reduce lower-extremity amputation in DM. It is known that reactive oxygen species (ROS) production and oxidative stress are significantly increased in DM, and excessive oxidative stress is closely involved in the development of diabetic complications, including cardiovascular diseases, nephropathy, and retinopathy. Although low levels of ROS function as signaling molecules to mediate various biological responses such as gene expression, cell proliferation, migration, angiogenesis, apoptosis, and senescence in endothelial cells (ECs), high levels of ROS could contribute to a variety of pathologic conditions, including reduced nitric oxide (NO) bioavailability, impairment of vascular function and other endothelial phenotypic abnormalities. The metabolic abnormalities in DM could cause mitochondrial superoxide overproduction in endothelial cells of both large and small vessels, as well as in the myocardium. Increased glucose levels could stimulate ROS production, leading to further glucose uptake and triggering cell toxicity and death. In addition, increased formation of advanced glycation end-products (AGEs) could enhance the activity of ROS-generating enzymes including NADPH oxidase, exacerbating oxidative stress and mitochondrial superoxide production. Thus, the objectives of the proposed study are: 1) to investigate the effect of NAC treatment on the outcomes in patients with advanced atherosclerotic heart diseases and not a candidate for revascularization; and 2) to investigate the effect of NAC treatment on the outcomes in diabetic patients with significant peripheral artery disease.
- Conditions
- Atherosclerosis of Artery, Peripheral Artery Disease, Diabetes Mellitus, Inflammation, Oxidative Stress
- Being tested
- N-acetylcysteine, Placebo
- Keywords
- Atherosclerosis, ROS, Inflammation, Diabetes
- Medical subject headings
- Peripheral Arterial Disease, Diabetes Mellitus, Inflammation, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Also called Acetadote
Will be used as capsule form, 600mg per day if the patient can tolerate it. If not, we may decrease the dosage.
PlaceboDrug
Similar chemical structure of NAC but without function
| Study group | Role | What they receive |
|---|---|---|
| NAC treatment | Active comparator | N-acetylcysteine capsule, 600mg/day, oral, 5 years Receives: Drug: N-acetylcysteine |
| Placebo | Placebo comparator | Similar chemical structure of NAC but without function Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of blood pressure over time points
Diastolic and systolic blood pressure
Measured: baseline, 3 months, 6 months, and 12 months
Change of biomarkers over time points
Blood samples (5ml) will be taken for biomarkers analysis (complete blood cell count [CBC], biochemistry, Thyroid stimulating hormone [TSH], renal function, C-reactive protein [CRP], IL-1β, IL-6, TNF-α, and lipids profiles).
Measured: baseline, 3 months, 6 months, and 12 months
Change of heart rate over time points
Number of beats per minute
Measured: 1 baseline, 3 months, 6 months, and 12 months
Change of body weight over time points
Measured in kg
Measured: baseline, 3 months, 6 months, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2023
- Study start15 Oct 2021
- Primary completion15 Oct 2021
- Study completion15 Oct 2021
Why it stopped: Lack of available resources needed to conduct study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Atherosclerosis of ArteryStudies of the same condition, open and under way.
- More trials run by University of Missouri-ColumbiaThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Missouri-Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- Shandong Provincial Hospital, Central South University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05908513
- Sponsor's protocol ID
- 2072662
- Acronym
- RENEWAL
- Status last verified
- Jun 2023
- First submitted
- 4 Oct 2021
- Last updated
- 18 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Due to the confidential information included in this study, all data won't be shared for now.
Publications
Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Shay CM, Spartano NL, Stokes A, Tirschwell DL, VanWagner LB, Tsao CW; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. 2020 Mar 3;141(9):e139-e596. doi: 10.1161/CIR.0000000000000757. Epub 2020 Jan 29.
PubMed 31992061Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007 Feb 28;297(8):842-57. doi: 10.1001/jama.297.8.842.
PubMed 17327526Thompson PL, Nidorf SM. Colchicine: an affordable anti-inflammatory agent for atherosclerosis. Curr Opin Lipidol. 2018 Dec;29(6):467-473. doi: 10.1097/MOL.0000000000000552.
PubMed 30320614Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ; CANTOS Trial Group. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017 Sep 21;377(12):1119-1131. doi: 10.1056/NEJMoa1707914. Epub 2017 Aug 27.
PubMed 28845751Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TSJ, The SHK, Xu XF, Ireland MA, Lenderink T, Latchem D, Hoogslag P, Jerzewski A, Nierop P, Whelan A, Hendriks R, Swart H, Schaap J, Kuijper AFM, van Hessen MWJ, Saklani P, Tan I, Thompson AG, Morton A, Judkins C, Bax WA, Dirksen M, Alings M, Hankey GJ, Budgeon CA, Tijssen JGP, Cornel JH, Thompson PL; LoDoCo2 Trial Investigators. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020 Nov 5;383(19):1838-1847. doi: 10.1056/NEJMoa2021372. Epub 2020 Aug 31.
PubMed 32865380Salamon S, Kramar B, Marolt TP, Poljsak B, Milisav I. Medical and Dietary Uses of N-Acetylcysteine. Antioxidants (Basel). 2019 Apr 28;8(5):111. doi: 10.3390/antiox8050111.
PubMed 31035402Voghel G, Thorin-Trescases N, Farhat N, Mamarbachi AM, Villeneuve L, Fortier A, Perrault LP, Carrier M, Thorin E. Chronic treatment with N-acetyl-cystein delays cellular senescence in endothelial cells isolated from a subgroup of atherosclerotic patients. Mech Ageing Dev. 2008 May;129(5):261-70. doi: 10.1016/j.mad.2008.01.004. Epub 2008 Jan 20.
PubMed 18302967Sung HJ, Kim J, Kim Y, Jang SW, Ko J. N-acetyl cysteine suppresses the foam cell formation that is induced by oxidized low density lipoprotein via regulation of gene expression. Mol Biol Rep. 2012 Mar;39(3):3001-7. doi: 10.1007/s11033-011-1062-1. Epub 2011 Jun 17.
PubMed 21681422Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Guyton RA, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK. Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Apr 2;127(13):1425-43. doi: 10.1161/CIR.0b013e31828b82aa. Epub 2013 Mar 1. No abstract available.
PubMed 23457117Hoffstad O, Mitra N, Walsh J, Margolis DJ. Diabetes, lower-extremity amputation, and death. Diabetes Care. 2015 Oct;38(10):1852-7. doi: 10.2337/dc15-0536. Epub 2015 Jul 22.
PubMed 26203063Geiss LS, Li Y, Hora I, Albright A, Rolka D, Gregg EW. Resurgence of Diabetes-Related Nontraumatic Lower-Extremity Amputation in the Young and Middle-Aged Adult U.S. Population. Diabetes Care. 2019 Jan;42(1):50-54. doi: 10.2337/dc18-1380. Epub 2018 Nov 8.
PubMed 30409811Malik RA, Tesfaye S, Ziegler D. Medical strategies to reduce amputation in patients with type 2 diabetes. Diabet Med. 2013 Aug;30(8):893-900. doi: 10.1111/dme.12169.
PubMed 23445087Howangyin KY, Silvestre JS. Diabetes mellitus and ischemic diseases: molecular mechanisms of vascular repair dysfunction. Arterioscler Thromb Vasc Biol. 2014 Jun;34(6):1126-35. doi: 10.1161/ATVBAHA.114.303090. Epub 2014 Mar 27.
PubMed 24675660Forrester SJ, Kikuchi DS, Hernandes MS, Xu Q, Griendling KK. Reactive Oxygen Species in Metabolic and Inflammatory Signaling. Circ Res. 2018 Mar 16;122(6):877-902. doi: 10.1161/CIRCRESAHA.117.311401.
PubMed 29700084Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010 Oct 29;107(9):1058-70. doi: 10.1161/CIRCRESAHA.110.223545.
PubMed 21030723
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Study on N-acetylcysteine Treatment and Outcomes in Patients With Advanced Atherosclerotic Heart Diseases and Diabetes Mellitus (RENEWAL)
- ClinicalTrials.gov ID
- NCT05908513
- Acronym / sponsor ID
- RENEWAL / 2072662
- Conditions
- Atherosclerosis of Artery, Peripheral Artery Disease, Diabetes Mellitus, Inflammation, Oxidative Stress
- Keywords
- Atherosclerosis, ROS, Inflammation, Diabetes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of available resources needed to conduct study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Missouri-ColumbiaUniversity, hospital or other
- Collaborators
- Shandong Provincial Hospital, Central South University
- Study start
- 15 Oct 2021 (actual)
- Primary completion
- 15 Oct 2021 (actual)
- Study completion
- 15 Oct 2021 (actual)
- First posted
- 18 Jun 2023 (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.
Atherosclerosis and diabetes are related to coronary artery disease and peripheral artery disease. The mechanisms are related to increased reactive oxygen species (ROS) formation and inflammatory cytokine secretion. However, simply using antioxidant or anti-inflammatory therapies has no optimal outcomes. On the other hand, N-acetylcysteine (NAC) which has both antioxidant and anti-inflammatory effects could effectively attenuate ROS production and reduce vascular inflammation. Hence, we will investigate the effect of NAC treatment on the outcomes in patients with advanced atherosclerotic heart diseases and patients with diabetes combined with significant peripheral artery disease.
Detailed description
Atherosclerosis is a chronic inflammatory disease and remains one of the major causes of death globally, despite aggressive risk stratifications including smoking cessation, optimal control of lipid, blood pressure, and diabetes. Antioxidant therapies with vitamin E and C or β-carotene failed to achieve significant clinical benefits in patients with cardiovascular diseases (CVD) including atherosclerosis. New therapies including interleukin-1β monoclonal antibody canakinumab and anti-inflammatory drug colchicine could significantly reduce the rate of major adverse cardiovascular events (MACE) including nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. However, canakinumab therapy did not decrease all-cause mortality, and was associated with a significant increase in the incidence of fatal infection (including sepsis), and high cost. While colchicine is a generic drug and decreases the rate of MACE, colchicine therapy is associated with a significant increase in death from non-cardiovascular causes5. Thus, alternative options are needed to attenuate atherosclerosis. N-acetylcysteine (NAC) has been traditionally considered an antioxidant although it is more like an anti-inflammatory agent, and could effectively attenuate reactive oxygen species (ROS) production, and reduce vascular inflammation. NAC significantly decreases the progression of atherosclerosis in young apolipoprotein E-deficient mice and low-density lipoprotein receptor deficient (LDLR-/-) mice with an atherogenic high fat diet (HFD). NAC treatment delays cellular senescence in endothelial cells from atherosclerotic patients, and improves coronary and peripheral endothelium-dependent vasodilation in human subjects with or without atherosclerosis. NAC treatment also inhibits oxidized LDL-induced foam cell formation and suppresses matrix-degrading capacity of foam cells. However, it is unclear if NAC could attenuate the progression of atherosclerosis or reverse the course of atherosclerosis in aging mice. Diabetes mellitus (DM) significantly increases the risk of developing severe peripheral artery disease (PAD) with critical limb ischemia (CLI) and chronic ulcers. Due to poor healing, patients with diabetic CLI may need limb amputation that accounts for about 60% of all non-traumatic amputations in the U. S. After a two decade reduction in diabetes-related non-traumatic lower-extremity amputation, recent data show an increase in amputation, particularly in young and middle-aged adults. In addition, major randomized clinical trials have shown that blood glucose-lowering or anti-hypertensive therapies have very limited effects on reducing macrovascular complications, and no benefit on amputation rates in diabetic patients. These highlight an urgent need for alterative effective approaches to promoting the recovery of diabetic ischemic limb to reduce lower-extremity amputation in DM. It is known that reactive oxygen species (ROS) production and oxidative stress are significantly increased in DM, and excessive oxidative stress is closely involved in the development of diabetic complications, including cardiovascular diseases, nephropathy, and retinopathy. Although low levels of ROS function as signaling molecules to mediate various biological responses such as gene expression, cell proliferation, migration, angiogenesis, apoptosis, and senescence in endothelial cells (ECs), high levels of ROS could contribute to a variety of pathologic conditions, including reduced nitric oxide (NO) bioavailability, impairment of vascular function and other endothelial phenotypic abnormalities. The metabolic abnormalities in DM could cause mitochondrial superoxide overproduction in endothelial cells of both large and small vessels, as well as in the myocardium. Increased glucose levels could stimulate ROS production, leading to further glucose uptake and triggering cell toxicity and death. In addition, increased formation of advanced glycation end-products (AGEs) could enhance the activity of ROS-generating enzymes including NADPH oxidase, exacerbating oxidative stress and mitochondrial superoxide production. Thus, the objectives of the proposed study are: 1) to investigate the effect of NAC treatment on the outcomes in patients with advanced atherosclerotic heart diseases and not a candidate for revascularization; and 2) to investigate the effect of NAC treatment on the outcomes in diabetic patients with significant peripheral artery disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NAC treatment | Active comparator | Drug: N-acetylcysteineN-acetylcysteine capsule, 600mg/day, oral, 5 years |
| Placebo | Placebo comparator | Drug: PlaceboSimilar chemical structure of NAC but without function |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 1) significant coronary artery disease (CAD) and not a candidate for revascularization (CABG or PCI), or 2) significant peripheral artery disease (PAD) with or without critical limb ischemia (CLI) or chronic ulcers.
Key exclusion criteria (8 listed)
- 1) Pregnant or nursing (lactating) women, confirmed by a positive hCG laboratory test 2). Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are a. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone or partial or total hysterectomy, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
- 3). Planned coronary revascularization (PCI or CABG) or any other major surgical procedure.
- 4). Major non-cardiac surgical or major endoscopic procedure within the past 6 months prior to the initial visit (Visit 1) 5). Multi-vessel CABG surgery within the past 3 years 6). Symptomatic patients with Class IV heart failure (HF) (New York Heart Association).
- 7). Uncontrolled hypertension (defined as an average SBP >180 mmHg or an average diastolic blood pressure (DBP) >110 mmHg at Visit 1. Patients are allowed to be re-evaluated, at the discretion of investigator for this criterion if anti-hypertensive therapy has been started or increased as a result of initial screening blood pressure above these limits.
- 8). Uncontrolled diabetes with persistent fasting blood glucose level of 300 or A1C of 7.5 for 3 months or defined by the investigator 9). Kidney or other organ transplant (due to anti-immune therapy) at Visit 1 10). Prior malignancy other than basal cell skin carcinoma. 11). A history of alcohol and/or substance abuse that could interfere with the conduct of the trial.
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 |
|---|---|---|
| N-acetylcysteineAlso: AcetadoteWill be used as capsule form, 600mg per day if the patient can tolerate it. If not, we may decrease the dosage. | Drug | NAC treatment |
| PlaceboSimilar chemical structure of NAC but without function | Drug | Placebo |
Primary outcome
Change of blood pressure over time points
Time frame: baseline, 3 months, 6 months, and 12 months
Diastolic and systolic blood pressure
Change of biomarkers over time points
Time frame: baseline, 3 months, 6 months, and 12 months
Blood samples (5ml) will be taken for biomarkers analysis (complete blood cell count [CBC], biochemistry, Thyroid stimulating hormone [TSH], renal function, C-reactive protein [CRP], IL-1β, IL-6, TNF-α, and lipids profiles).
Change of heart rate over time points
Time frame: 1 baseline, 3 months, 6 months, and 12 months
Number of beats per minute
Change of body weight over time points
Time frame: baseline, 3 months, 6 months, and 12 months
Measured in kg
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2023.
- Background: PubMed 31992061Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Shay CM, Spartano NL, Stokes A, Tirschwell DL, VanWagner LB, Tsao CW; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. 2020 Mar 3;141(9):e139-e596. doi: 10.1161/CIR.0000000000000757. Epub 2020 Jan 29.
- Background: PubMed 17327526Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007 Feb 28;297(8):842-57. doi: 10.1001/jama.297.8.842.
- Background: PubMed 30320614Thompson PL, Nidorf SM. Colchicine: an affordable anti-inflammatory agent for atherosclerosis. Curr Opin Lipidol. 2018 Dec;29(6):467-473. doi: 10.1097/MOL.0000000000000552.
- Background: PubMed 28845751Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ; CANTOS Trial Group. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017 Sep 21;377(12):1119-1131. doi: 10.1056/NEJMoa1707914. Epub 2017 Aug 27.
- Background: PubMed 32865380Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TSJ, The SHK, Xu XF, Ireland MA, Lenderink T, Latchem D, Hoogslag P, Jerzewski A, Nierop P, Whelan A, Hendriks R, Swart H, Schaap J, Kuijper AFM, van Hessen MWJ, Saklani P, Tan I, Thompson AG, Morton A, Judkins C, Bax WA, Dirksen M, Alings M, Hankey GJ, Budgeon CA, Tijssen JGP, Cornel JH, Thompson PL; LoDoCo2 Trial Investigators. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020 Nov 5;383(19):1838-1847. doi: 10.1056/NEJMoa2021372. Epub 2020 Aug 31.
- Background: PubMed 31035402Salamon S, Kramar B, Marolt TP, Poljsak B, Milisav I. Medical and Dietary Uses of N-Acetylcysteine. Antioxidants (Basel). 2019 Apr 28;8(5):111. doi: 10.3390/antiox8050111.
- Background: PubMed 18302967Voghel G, Thorin-Trescases N, Farhat N, Mamarbachi AM, Villeneuve L, Fortier A, Perrault LP, Carrier M, Thorin E. Chronic treatment with N-acetyl-cystein delays cellular senescence in endothelial cells isolated from a subgroup of atherosclerotic patients. Mech Ageing Dev. 2008 May;129(5):261-70. doi: 10.1016/j.mad.2008.01.004. Epub 2008 Jan 20.
- Background: PubMed 21681422Sung HJ, Kim J, Kim Y, Jang SW, Ko J. N-acetyl cysteine suppresses the foam cell formation that is induced by oxidized low density lipoprotein via regulation of gene expression. Mol Biol Rep. 2012 Mar;39(3):3001-7. doi: 10.1007/s11033-011-1062-1. Epub 2011 Jun 17.
- Background: PubMed 23457117Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Guyton RA, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK. Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Apr 2;127(13):1425-43. doi: 10.1161/CIR.0b013e31828b82aa. Epub 2013 Mar 1. No abstract available.
- Background: PubMed 26203063Hoffstad O, Mitra N, Walsh J, Margolis DJ. Diabetes, lower-extremity amputation, and death. Diabetes Care. 2015 Oct;38(10):1852-7. doi: 10.2337/dc15-0536. Epub 2015 Jul 22.
- Background: PubMed 30409811Geiss LS, Li Y, Hora I, Albright A, Rolka D, Gregg EW. Resurgence of Diabetes-Related Nontraumatic Lower-Extremity Amputation in the Young and Middle-Aged Adult U.S. Population. Diabetes Care. 2019 Jan;42(1):50-54. doi: 10.2337/dc18-1380. Epub 2018 Nov 8.
- Background: PubMed 23445087Malik RA, Tesfaye S, Ziegler D. Medical strategies to reduce amputation in patients with type 2 diabetes. Diabet Med. 2013 Aug;30(8):893-900. doi: 10.1111/dme.12169.
- Individual participant dataSharing planned: No. Due to the confidential information included in this study, all data won't be shared for now.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing N-acetylcysteine in people with Atherosclerosis of Artery and Peripheral Artery Disease, run by University of Missouri-Columbia at 2 sites in China.
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 1 inclusion and 8 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: withdrawn, as of the sponsor's last update on 18 Jun 2023. 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 China. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Change of blood pressure over time points (time frame: baseline, 3 months, 6 months, and 12 months). The study lists 4 primary outcomes in all. 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 NCT05908513, which also lists 21 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 18 Jun 2023.