Diabetes MellitusEarly Phase 1NCT03253328
N-Acetyl-Cysteine (NAC) for Healing of Amputation Stumps in the Setting of Diabetes
A Early Phase 1 study testing Active Arm N-acetyl cysteine (NAC) in people with Diabetes Mellitus and Critical Limb Ischemia, run by Washington University School of Medicine at 1 site in United States.
Trial summary
In this pilot clinical study the investigators propose to conduct a prospective, randomized, double-blinded, placebo-controlled clinical trial for 30 days for participants with critical limb ischemia (CLI) who undergo a major (above-knee or below-knee) lower extremity amputation. Read more about this study
- Who is it for?
- Ages 30 to 90 years
- Conditions the study is for
- Diabetes Mellitus, Critical Limb Ischemia, Lower Limb Amputation Knee
- What is being tested?
- Active Arm N-acetyl cysteine (NAC)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2017to 27 Jun 2022
- Phase
- Early Phase 1
- 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 30 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject undergoing elective major (above-knee or below-knee) lower extremity amputation for CLI
- Both male and female patients
- All ethnic groups
- Between of the ages of 30-90 years old
- Adequate nutritional status - defined as BMI > 19
Who cannot join
- Pregnant women, and women who are breastfeeding
- Known history of end-stage liver disease
- Severe asthma
- Heavy alcohol consumption (male > 2 drinks per day and women > 1 drink per day)
- Individuals actively receiving chemotherapy.
- Anticipated enrollment in another study that investigates another drug agent within 30 days from enrollment in this study.
Show all 10Show fewer
- Patients receiving carbamazepine.
- Severe anemia (HCT < 22).
- Allergy to either NAC or Indocyanine Green (ICG).
- Patients with open wound(s) from a prior amputation on the ipsilateral limb (excluding patients who had prior partial foot amputation, who are now requiring a below-knee or above-knee amputation).
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: N-Acetyl-Cysteine for Healing of Amputation Stumps in the Setting of Diabetes
In this pilot clinical study the investigators propose to conduct a prospective, randomized, double-blinded, placebo-controlled clinical trial for 30 days for participants with critical limb ischemia (CLI) who undergo a major (above-knee or below-knee) lower extremity amputation. By exploring the primary endpoints we aim to determine whether NAC can affect amputation stump perfusion and healing. Based on preclinical data, the investigators hypothesize that NAC will augment both amputation stump perfusion as well as healing. The investigators will utilize the data from this trial to determine the true effect size that is necessary for a larger clinical trial to determine the clinical efficacy of NAC is healing surgical sites such as major lower extremity amputation stumps.
Read the detailed description
In this pilot clinical study the investigators propose to conduct a prospective, randomized, double-blinded, placebo-controlled clinical trial, in 50 participants with CLI who have undergone a major (above-knee or below-knee) lower extremity amputation. 25 participants will receive NAC 1200mg intravenously twice a day for 6 consecutive days following amputation. 25 participants will receive placebo saline intravenous infusion twice a day for 6 days following amputation. Post-amputation participants will be monitored for specific anthropometric parameters and stump perfusion assessments (using laser-assisted fluorescent angiography and transcutaneous oxygen pressure measurement). The primary study endpoints are to determine if lower extremity stump healing and perfusion are affected by perioperative NAC administration. A secondary endpoint will be to determine the effect size that would be necessary to power a larger clinical trial to determine whether NAC treatment can affect tissue perfusion and healing at major lower extremity amputation stumps in participants with CLI.
- Conditions
- Diabetes Mellitus, Critical Limb Ischemia, Lower Limb Amputation Knee, Peripheral Arterial Disease
- Being tested
- Active Arm N-acetyl cysteine (NAC), Placebo Arm
- Medical subject headings
- Diabetes Mellitus, Chronic Limb-Threatening Ischemia, Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Arm N-acetyl cysteine (NAC)Drug
Also called N-acetyl cysteine (NAC)
N-acetyl cysteine (NAC) 1200mg twice a day for 6 days post-amputation
Placebo ArmDrug
Also called Placebo 1/2 normal saline infusion
Placebo 1/2 normal saline infusion twice a day for 6 days post-amputation
| Study group | Role | What they receive |
|---|---|---|
| Active Arm N-acetyl cysteine (NAC) | Active comparator | Upon study enrollment, patients will be randomized 1:1 by Investigational Pharmacy to a standard adult intravenous dose of NAC (1200mg twice a day) for 6 days post-amputation. Receives: Drug: Active Arm N-acetyl cysteine (NAC) |
| Placebo Arm | Placebo comparator | Upon study enrollment, patients will be randomized 1:1 by Investigational Pharmacy to placebo ½ normal saline infusion (twice a day) for 6 days post-amputation. Receives: Drug: Placebo Arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Postoperative Laser-Assisted Fluorescent Angiography (LAFA) Perfusion.
Images were collected from the SPY Elite LAFA apparatus. Regions of interest were drawn in a standardized fashion around either the incision or the whole amputation stump. NIH image J software was used to evaluate peak perfusion signal intensity in all regions of interest. Change in LAFA was assessed at postoperative day (POD) 0, 3, and 5. Fold change in % perfusion in the ROI's between POD 0/3/5 was determined and compared between study groups. The primary outcomes were change in postoperative Laser-Assisted Fluorescent Angiography (LAFA) perfusion at POD3 and POD5 and stump healing at postoperative day 30 (POD30).
Measured: Day 0, Day 3, Day 5
Stump Healing Assessment at Postoperative Day (POD) 30.
Amputation stump photographs were serially obtained for all study patients immediately before LAFA assessments on POD 0, 3, and 5. A blinded observer evaluated amputation stump incision healing using a modified Bates-Jensen Score (mBJS) wound assessment tool. As previously described, the amputation stumps were evaluated on the following criteria: amputation stump skin color, epithelialization, amount of exudate, and the presence and volume of eschar. Each wound healing characteristic was given a score of 1 to 5, with higher scores indicating worse healing. Eschar volume was determined using ImageJ software. Aggregate mBJS scores were derived for both the whole stump and along the suture line. Clinical amputation stump healing was determined by the surgeon at follow-up clinical evaluations up until POD30.
De Silva GS, Saffaf K, Sanchez LA, et al. Amputation stump perfusion is predictive of post-operative necrotic eschar formation. Am J Surg. 2018;216:540-546.
Measured: 30 days
Secondary outcomes (1)
Amputation Stump Perfusion in High Risk Patients
POD0 LAFA was evaluated for all patients and patients that demonstrated amputation stump peak perfusion defects were considered high risk. Within these patients we then evaluated amputation stump perfusion at POD5.
Change in perfusion over this time was compared between the study groups.
Measured: POD5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2017
- Study start1 Mar 2017
- Primary completion31 Aug 2021
- Study completion27 Jun 2022
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 (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mohamed Zayed, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03253328
- Sponsor's protocol ID
- 201611065
- Status last verified
- Mar 2024
- First submitted
- 17 Mar 2017
- Last updated
- 16 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lee JV, Engel C, Tay S, DeSilva G, Desai K, Cashin J, Semenkovich CF, Zayed MA. Impact of N-Acetyl-Cysteine on Ischemic Stumps Following Major Lower Extremity Amputation: A Pilot Randomized Clinical Trial. Ann Surg. 2022 Nov 1;276(5):e302-e310. doi: 10.1097/SLA.0000000000005389. Epub 2022 Jan 24.
PubMed 35129469
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- N-Acetyl-Cysteine for Healing of Amputation Stumps in the Setting of Diabetes
- ClinicalTrials.gov ID
- NCT03253328
- Acronym / sponsor ID
- 201611065
- Conditions
- Diabetes Mellitus, Critical Limb Ischemia, Lower Limb Amputation Knee, Peripheral Arterial Disease
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 31 Aug 2021 (actual)
- Study completion
- 27 Jun 2022 (actual)
- First posted
- 17 Aug 2017 (actual)
- Results
- Posted 16 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this pilot clinical study the investigators propose to conduct a prospective, randomized, double-blinded, placebo-controlled clinical trial for 30 days for participants with critical limb ischemia (CLI) who undergo a major (above-knee or below-knee) lower extremity amputation. By exploring the primary endpoints we aim to determine whether NAC can affect amputation stump perfusion and healing. Based on preclinical data, the investigators hypothesize that NAC will augment both amputation stump perfusion as well as healing. The investigators will utilize the data from this trial to determine the true effect size that is necessary for a larger clinical trial to determine the clinical efficacy of NAC is healing surgical sites such as major lower extremity amputation stumps.
Detailed description
In this pilot clinical study the investigators propose to conduct a prospective, randomized, double-blinded, placebo-controlled clinical trial, in 50 participants with CLI who have undergone a major (above-knee or below-knee) lower extremity amputation. 25 participants will receive NAC 1200mg intravenously twice a day for 6 consecutive days following amputation. 25 participants will receive placebo saline intravenous infusion twice a day for 6 days following amputation. Post-amputation participants will be monitored for specific anthropometric parameters and stump perfusion assessments (using laser-assisted fluorescent angiography and transcutaneous oxygen pressure measurement). The primary study endpoints are to determine if lower extremity stump healing and perfusion are affected by perioperative NAC administration. A secondary endpoint will be to determine the effect size that would be necessary to power a larger clinical trial to determine whether NAC treatment can affect tissue perfusion and healing at major lower extremity amputation stumps in participants with CLI.
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 |
|---|---|---|
| Active Arm N-acetyl cysteine (NAC) | Active comparator | Drug: Active Arm N-acetyl cysteine (NAC)Upon study enrollment, patients will be randomized 1:1 by Investigational Pharmacy to a standard adult intravenous dose of NAC (1200mg twice a day) for 6 days post-amputation. |
| Placebo Arm | Placebo comparator | Drug: Placebo ArmUpon study enrollment, patients will be randomized 1:1 by Investigational Pharmacy to placebo ½ normal saline infusion (twice a day) for 6 days post-amputation. |
Who may qualify
- Ages
- 30 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subject undergoing elective major (above-knee or below-knee) lower extremity amputation for CLI
- Both male and female patients
- All ethnic groups
- Between of the ages of 30-90 years old
- Adequate nutritional status - defined as BMI > 19
Key exclusion criteria (10 listed)
- Pregnant women, and women who are breastfeeding
- Known history of end-stage liver disease
- Severe asthma
- Heavy alcohol consumption (male > 2 drinks per day and women > 1 drink per day)
- Individuals actively receiving chemotherapy.
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 |
|---|---|---|
| Active Arm N-acetyl cysteine (NAC)Also: N-acetyl cysteine (NAC)N-acetyl cysteine (NAC) 1200mg twice a day for 6 days post-amputation | Drug | Active Arm N-acetyl cysteine (NAC) |
| Placebo ArmAlso: Placebo 1/2 normal saline infusionPlacebo 1/2 normal saline infusion twice a day for 6 days post-amputation | Drug | Placebo Arm |
Primary outcome
Change in Postoperative Laser-Assisted Fluorescent Angiography (LAFA) Perfusion.
Time frame: Day 0, Day 3, Day 5
Images were collected from the SPY Elite LAFA apparatus. Regions of interest were drawn in a standardized fashion around either the incision or the whole amputation stump. NIH image J software was used to evaluate peak perfusion signal intensity in all regions of interest. Change in LAFA was assessed at postoperative day (POD) 0, 3, and 5. Fold change in % perfusion in the ROI's between POD 0/3/5 was determined and compared between study groups. The primary outcomes were change in postoperative Laser-Assisted Fluorescent Angiography (LAFA) perfusion at POD3 and POD5 and stump healing at postoperative day 30 (POD30).
Stump Healing Assessment at Postoperative Day (POD) 30.
Time frame: 30 days
Amputation stump photographs were serially obtained for all study patients immediately before LAFA assessments on POD 0, 3, and 5. A blinded observer evaluated amputation stump incision healing using a modified Bates-Jensen Score (mBJS) wound assessment tool. As previously described, the amputation stumps were evaluated on the following criteria: amputation stump skin color, epithelialization, amount of exudate, and the presence and volume of eschar. Each wound healing characteristic was given a score of 1 to 5, with higher scores indicating worse healing. Eschar volume was determined using ImageJ software. Aggregate mBJS scores were derived for both the whole stump and along the suture line. Clinical amputation stump healing was determined by the surgeon at follow-up clinical evaluations up until POD30. De Silva GS, Saffaf K, Sanchez LA, et al. Amputation stump perfusion is predictive of post-operative necrotic eschar formation. Am J Surg. 2018;216:540-546.
1 secondary outcome
Amputation Stump Perfusion in High Risk Patients
Time frame: POD5
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35129469Lee JV, Engel C, Tay S, DeSilva G, Desai K, Cashin J, Semenkovich CF, Zayed MA. Impact of N-Acetyl-Cysteine on Ischemic Stumps Following Major Lower Extremity Amputation: A Pilot Randomized Clinical Trial. Ann Surg. 2022 Nov 1;276(5):e302-e310. doi: 10.1097/SLA.0000000000005389. Epub 2022 Jan 24.
- Individual participant dataSharing planned: No
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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.
Mohamed Zayed, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Active Arm N-acetyl cysteine (NAC) in people with Diabetes Mellitus and Critical Limb Ischemia, run by Washington University School of Medicine 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 5 inclusion and 10 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 16 Aug 2024. 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 phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 16 Aug 2024). 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?
Change in Postoperative Laser-Assisted Fluorescent Angiography (LAFA) Perfusion. (time frame: Day 0, Day 3, Day 5). The study lists 2 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 NCT03253328, which also lists 1 linked publication.
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 16 Aug 2024.