Graft RejectionPhase 2NCT04488094
Diagnostic Validity of [18F]FSPG PET for the Assessment of Acute Rejection After Heart or Liver Transplantation
A Phase 2 study testing [18F]FSPG in people with Graft Rejection and Heart Transplantation, run by Asan Medical Center at 1 site in South Korea.
Trial summary
The a series of clinical studies of [18F]FSPG PET/CT showed that [18F]FSPG is safe and promising PET tracer for detecting inflammation with favorable biodistribution and pharmacokinetics in patients. Read more about this study
- Who is it for?
- Ages 19 to 79 years
- Conditions the study is for
- Graft Rejection, Heart Transplantation, Liver Transplantation
- What is being tested?
- [18F]FSPG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteSouth Korea
- Study dates
- 18 Nov 2020to 31 Mar 2023
- Phase
- Phase 2
- 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 19 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is aged between 19 and 79 years and male or female of any race/ethnicity.
- Subject received heart transplantation or liver transplantation at least 30 days prior to screening
- Subject underwent or is scheduled to undergo biopsy for histologic diagnosis of acute rejection within 7 days prior to or after the planned [18F]FSPG PET/CT administration.
Who cannot join
- Subject or subject's legally acceptable representative does not provide written informed consent.
- Dose escalation of the current immunosuppressant drugs or starting a new immunosuppressant is scheduled from the study enrollment to the scheduled day of biopsy, or 24 hours after [18F]FSPG administration
- Female subject is pregnant or nursing. Exclusion of the possibility of pregnancy is made by one of the following: 1) Woman is physiologically post-menopausal (cessation of menses for more than 2 years), 2) woman is surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy, or 3) if the woman is of childbearing potential, a serum or urine pregnancy test performed within 24 hours immediately prior to administration of [18F]FSPG has to be negative and the women is advised to apply contraceptive measures during her participation in this study.
- Subject has concurrent severe and/or uncontrolled and/or unstable medical disease (e.g. congestive heart failure, acute myocardial infarction, severe pulmonary disease, chronic renal or hepatic disease which could compromise participation in the study) in the judgment of the investigator.
- Subject is a relative of the investigator, student of the investigator or otherwise dependent.
- Subject has received any investigational drugs or devices within four weeks prior to the study enrollment or within 24 hours after administration of [18F]FSPG.
- Subject has been previously included in this study.
- Subject has any other condition or personal circumstances that, in the judgment of the investigator, might make collection of complete data difficult or impossible.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2, Open-label, Non-randomized, Single Center Study to Explore Diagnostic Performance of [18F]FSPG PET/CT for the Assessment of Acute Allograft Rejection After Heart or Liver Transplantation
The a series of clinical studies of [18F]FSPG PET/CT showed that [18F]FSPG is safe and promising PET tracer for detecting inflammation with favorable biodistribution and pharmacokinetics in patients. By using [18F]FSPG, which targets system xCˉ, a key player in the active phase of inflammation, the goal of this phase 2 study is to evaluate diagnostic validity of [18F]FSPG PET/CT to detect allograft rejection after heart and liver allograft, where conventional imaging has limitations. Diagnostic efficacy of [18F]FSPG PET/CT will be determined in comparison with histologic evaluation of allograft biopsy. Other critical questions including whether quantitative measures of [18F]FSPG uptake is associated with the severity of rejection, inter-reader variability of [18F]FSPG PET/CT, and safety assessment will be also evaluated.
Read the detailed description
This open label, non-randomized, single center, single-dose exploratory study is designed to obtain imaging assessments using PET/CT with [18F]FSPG in patients with heart transplantation (HT, n = 10) and liver transplantation (LT, n = 10). Subjects who underwent or scheduled to undergo biopsy for histologic diagnosis of acute rejection will be enrolled.
The study comprises 3 periods: screening, treatment, and follow-up. The screening period starts with the subject's signature on the informed consent form and ends with assignment to treatment that is inclusion of the subject for treatment. The treatment period starts with baseline measurements, and ends with the last measurement/procedure on the day following injection of 200 MBq of [18F]FSPG. The follow-up period contains the end-of-study interview. Key measurement is the PET/CT image acquisition about one hour after the single injection of [18F]FSPG. For evaluation of safety, adverse events (AE) will be monitored and recorded during the study period.
This study will be monitored regularly by a clinical research associate from the sponsor or a designated contract research organization. Data quality and study integrity will be assessed. The investigator will document the items that are required to evaluate the study in the subject files. Data required according to this protocol are to be recorded on the case report forms provided by the sponsor as soon as possible.
- Being tested
- [18F]FSPG
- Keywords
- Graft Rejection, Heart Transplantation, Liver Transplantation, Positron-Emission Tomography, Diagnostic Imaging
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]FSPGDrug
Also called FSPG
A radioactive dose of 200 MBq of the study drug with a total quantity of ≤ 100 µg will be administered as slow intravenous bolus injection over up to 60 seconds. PET/CT examinations will be performed at 60-75 min after the administration of [18F]FSPG.
| Study group | Role | What they receive |
|---|---|---|
| Heart transplantation | Experimental | Patients suspected of having acute heart allograft rejection after heart transplantation will receive a single IV injection of [18F]FSPG Receives: Drug: [18F]FSPG |
| Liver transplantation | Experimental | Patients suspected of having acute liver allograft rejection after heart transplantation will receive a single IV injection of [18F]FSPG Receives: Drug: [18F]FSPG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity and specificity of qualitative [18F]FSPG PET/CT interpretation for the diagnosis of patients with histologic evidence of acute allograft rejection
sensitivity = (the number of [18F]FSPG PET/CT-positive patients divided by the number of rejection positive patients on the histological evaluation) x 100; specificity = (the number of [18F]FSPG PET/CT-negative patients divided by the number of rejection negative patients on the histological evaluation) x 100
Measured: within 7 days of [18F]FSPG PET/CT
Secondary outcomes (8)
Association between quantitative [18F]FSPG uptake and histologic grade of rejection
The association between [18F]FSPG uptake and the histologic grades of rejection activity using Pearson or Spearman rank correlation coefficient
Measured: within 7 days of [18F]FSPG PET/CT
Inter-reader variability
Inter-reader variability of [18F]FSPG uptake score measured using the kappa statistic
Measured: within 1 day of [18F]FSPG PET/CT
Incidence of treatment emergent adverse events
Number of participants with treatment emergent adverse events graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0)
Measured: From the administration of [18F]FSPG to one day after [18F]FSPG PET/CT
Blood pressure
mmHg
Measured: Pre-treatment and three hours after the administration of [18F]FSPG
Heart rate
beats/minute
Measured: Pre-treatment and three hours after the administration of [18F]FSPG
Body temperature
Celsius
Measured: Pre-treatment and three hours after the administration of [18F]FSPG
Physical examination
The limited physical examination will comprise: general appearance, skin, neck, lungs, heart, abdomen, and a limited neurological examination (mental status, motor strength and sensor perception)
Measured: Pre-treatment and three hours after the administration of [18F]FSPG
Blood tests for safety
The clinical laboratory safety parameters to be assessed are as follows: glutamate pyruvate transaminase (GPT/ALAT), glutamate-oxaloacetate transaminase (GOT/ASAT), alkaline phosphatase, total bilirubin, creatinine, potassium, sodium, total protein, blood urea nitrogen (BUN), albumin
Measured: Pre-treatment and three hours after the administration of [18F]FSPG
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2020
- Study start18 Nov 2020
- Primary completion31 Mar 2023
- Study completion31 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Graft RejectionStudies of the same condition, open and under way.
- More trials run by Asan Medical CenterThe 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 2
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Patients suspected of having acute allograft rejection after heart transplantation (HT, n = 10) or liver transplantation (LT, n = 10)
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dae Hyuk Moon, Asan Medical Center
- Investigators
- Dae Hyuk Moon, MD, Principal investigator, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04488094
- Sponsor's protocol ID
- FSPG-1902
- Status last verified
- Jul 2023
- First submitted
- 23 Jul 2020
- Last updated
- 20 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Koglin N, Mueller A, Berndt M, Schmitt-Willich H, Toschi L, Stephens AW, Gekeler V, Friebe M, Dinkelborg LM. Specific PET imaging of xC- transporter activity using a (1)(8)F-labeled glutamate derivative reveals a dominant pathway in tumor metabolism. Clin Cancer Res. 2011 Sep 15;17(18):6000-11. doi: 10.1158/1078-0432.CCR-11-0687. Epub 2011 Jul 12.
PubMed 21750203Chae SY, Choi CM, Shim TS, Park Y, Park CS, Lee HS, Lee SJ, Oh SJ, Kim SY, Baek S, Koglin N, Stephens AW, Dinkelborg LM, Moon DH. Exploratory Clinical Investigation of (4S)-4-(3-18F-Fluoropropyl)-L-Glutamate PET of Inflammatory and Infectious Lesions. J Nucl Med. 2016 Jan;57(1):67-9. doi: 10.2967/jnumed.115.164020. Epub 2015 Oct 15.
PubMed 26471694Baek S, Choi CM, Ahn SH, Lee JW, Gong G, Ryu JS, Oh SJ, Bacher-Stier C, Fels L, Koglin N, Hultsch C, Schatz CA, Dinkelborg LM, Mittra ES, Gambhir SS, Moon DH. Exploratory clinical trial of (4S)-4-(3-[18F]fluoropropyl)-L-glutamate for imaging xC- transporter using positron emission tomography in patients with non-small cell lung or breast cancer. Clin Cancer Res. 2012 Oct 1;18(19):5427-37. doi: 10.1158/1078-0432.CCR-12-0214. Epub 2012 Aug 14.
PubMed 22893629Baek S, Mueller A, Lim YS, Lee HC, Lee YJ, Gong G, Kim JS, Ryu JS, Oh SJ, Lee SJ, Bacher-Stier C, Fels L, Koglin N, Schatz CA, Dinkelborg LM, Moon DH. (4S)-4-(3-18F-fluoropropyl)-L-glutamate for imaging of xC transporter activity in hepatocellular carcinoma using PET: preclinical and exploratory clinical studies. J Nucl Med. 2013 Jan;54(1):117-23. doi: 10.2967/jnumed.112.108704. Epub 2012 Dec 11.
PubMed 23232273
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open-label, Non-randomized, Single Center Study to Explore Diagnostic Performance of [18F]FSPG PET/CT for the Assessment of Acute Allograft Rejection After Heart or Liver Transplantation
- ClinicalTrials.gov ID
- NCT04488094
- Acronym / sponsor ID
- FSPG-1902
- Keywords
- Graft Rejection, Heart Transplantation, Liver Transplantation, Positron-Emission Tomography, Diagnostic Imaging
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Study start
- 18 Nov 2020 (actual)
- Primary completion
- 31 Mar 2023 (actual)
- Study completion
- 31 Mar 2023 (actual)
- First posted
- 27 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The a series of clinical studies of [18F]FSPG PET/CT showed that [18F]FSPG is safe and promising PET tracer for detecting inflammation with favorable biodistribution and pharmacokinetics in patients. By using [18F]FSPG, which targets system xCˉ, a key player in the active phase of inflammation, the goal of this phase 2 study is to evaluate diagnostic validity of [18F]FSPG PET/CT to detect allograft rejection after heart and liver allograft, where conventional imaging has limitations. Diagnostic efficacy of [18F]FSPG PET/CT will be determined in comparison with histologic evaluation of allograft biopsy. Other critical questions including whether quantitative measures of [18F]FSPG uptake is associated with the severity of rejection, inter-reader variability of [18F]FSPG PET/CT, and safety assessment will be also evaluated.
Detailed description
This open label, non-randomized, single center, single-dose exploratory study is designed to obtain imaging assessments using PET/CT with [18F]FSPG in patients with heart transplantation (HT, n = 10) and liver transplantation (LT, n = 10). Subjects who underwent or scheduled to undergo biopsy for histologic diagnosis of acute rejection will be enrolled.
The study comprises 3 periods: screening, treatment, and follow-up. The screening period starts with the subject's signature on the informed consent form and ends with assignment to treatment that is inclusion of the subject for treatment. The treatment period starts with baseline measurements, and ends with the last measurement/procedure on the day following injection of 200 MBq of [18F]FSPG. The follow-up period contains the end-of-study interview. Key measurement is the PET/CT image acquisition about one hour after the single injection of [18F]FSPG. For evaluation of safety, adverse events (AE) will be monitored and recorded during the study period.
This study will be monitored regularly by a clinical research associate from the sponsor or a designated contract research organization. Data quality and study integrity will be assessed. The investigator will document the items that are required to evaluate the study in the subject files. Data required according to this protocol are to be recorded on the case report forms provided by the sponsor as soon as possible.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients suspected of having acute allograft rejection after heart transplantation (HT, n = 10) or liver transplantation (LT, n = 10)
| Arm | Type | Receives |
|---|---|---|
| Heart transplantation | Experimental | Drug: [18F]FSPGPatients suspected of having acute heart allograft rejection after heart transplantation will receive a single IV injection of [18F]FSPG |
| Liver transplantation | Experimental | Drug: [18F]FSPGPatients suspected of having acute liver allograft rejection after heart transplantation will receive a single IV injection of [18F]FSPG |
Who may qualify
- Ages
- 19 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Subject is aged between 19 and 79 years and male or female of any race/ethnicity.
- Subject received heart transplantation or liver transplantation at least 30 days prior to screening
- Subject underwent or is scheduled to undergo biopsy for histologic diagnosis of acute rejection within 7 days prior to or after the planned [18F]FSPG PET/CT administration.
Key exclusion criteria (8 listed)
- Subject or subject's legally acceptable representative does not provide written informed consent.
- Dose escalation of the current immunosuppressant drugs or starting a new immunosuppressant is scheduled from the study enrollment to the scheduled day of biopsy, or 24 hours after [18F]FSPG administration
- Female subject is pregnant or nursing. Exclusion of the possibility of pregnancy is made by one of the following: 1) Woman is physiologically post-menopausal (cessation of menses for more than 2 years), 2) woman is surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy, or 3) if the woman is of childbearing potential, a serum or urine pregnancy test performed within 24 hours immediately prior to administration of [18F]FSPG has to be negative and the women is advised to apply contraceptive measures during her participation in this study.
- Subject has concurrent severe and/or uncontrolled and/or unstable medical disease (e.g. congestive heart failure, acute myocardial infarction, severe pulmonary disease, chronic renal or hepatic disease which could compromise participation in the study) in the judgment of the investigator.
- Subject is a relative of the investigator, student of the investigator or otherwise dependent.
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 |
|---|---|---|
| [18F]FSPGAlso: FSPGA radioactive dose of 200 MBq of the study drug with a total quantity of ≤ 100 µg will be administered as slow intravenous bolus injection over up to 60 seconds. PET/CT examinations will be performed at 60-75 min after the administration of [18F]FSPG. | Drug | Heart transplantation, Liver transplantation |
Primary outcome
Sensitivity and specificity of qualitative [18F]FSPG PET/CT interpretation for the diagnosis of patients with histologic evidence of acute allograft rejection
Time frame: within 7 days of [18F]FSPG PET/CT
sensitivity = (the number of [18F]FSPG PET/CT-positive patients divided by the number of rejection positive patients on the histological evaluation) x 100; specificity = (the number of [18F]FSPG PET/CT-negative patients divided by the number of rejection negative patients on the histological evaluation) x 100
8 secondary outcomes
Association between quantitative [18F]FSPG uptake and histologic grade of rejection
Time frame: within 7 days of [18F]FSPG PET/CT
Inter-reader variability
Time frame: within 1 day of [18F]FSPG PET/CT
Incidence of treatment emergent adverse events
Time frame: From the administration of [18F]FSPG to one day after [18F]FSPG PET/CT
Blood pressure
Time frame: Pre-treatment and three hours after the administration of [18F]FSPG
Heart rate
Time frame: Pre-treatment and three hours after the administration of [18F]FSPG
Body temperature
Time frame: Pre-treatment and three hours after the administration of [18F]FSPG
Physical examination
Time frame: Pre-treatment and three hours after the administration of [18F]FSPG
Blood tests for safety
Time frame: Pre-treatment and three hours after the administration of [18F]FSPG
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 20 Jul 2023.
- Background: PubMed 21750203Koglin N, Mueller A, Berndt M, Schmitt-Willich H, Toschi L, Stephens AW, Gekeler V, Friebe M, Dinkelborg LM. Specific PET imaging of xC- transporter activity using a (1)(8)F-labeled glutamate derivative reveals a dominant pathway in tumor metabolism. Clin Cancer Res. 2011 Sep 15;17(18):6000-11. doi: 10.1158/1078-0432.CCR-11-0687. Epub 2011 Jul 12.
- Background: PubMed 26471694Chae SY, Choi CM, Shim TS, Park Y, Park CS, Lee HS, Lee SJ, Oh SJ, Kim SY, Baek S, Koglin N, Stephens AW, Dinkelborg LM, Moon DH. Exploratory Clinical Investigation of (4S)-4-(3-18F-Fluoropropyl)-L-Glutamate PET of Inflammatory and Infectious Lesions. J Nucl Med. 2016 Jan;57(1):67-9. doi: 10.2967/jnumed.115.164020. Epub 2015 Oct 15.
- Background: PubMed 22893629Baek S, Choi CM, Ahn SH, Lee JW, Gong G, Ryu JS, Oh SJ, Bacher-Stier C, Fels L, Koglin N, Hultsch C, Schatz CA, Dinkelborg LM, Mittra ES, Gambhir SS, Moon DH. Exploratory clinical trial of (4S)-4-(3-[18F]fluoropropyl)-L-glutamate for imaging xC- transporter using positron emission tomography in patients with non-small cell lung or breast cancer. Clin Cancer Res. 2012 Oct 1;18(19):5427-37. doi: 10.1158/1078-0432.CCR-12-0214. Epub 2012 Aug 14.
- Background: PubMed 23232273Baek S, Mueller A, Lim YS, Lee HC, Lee YJ, Gong G, Kim JS, Ryu JS, Oh SJ, Lee SJ, Bacher-Stier C, Fels L, Koglin N, Schatz CA, Dinkelborg LM, Moon DH. (4S)-4-(3-18F-fluoropropyl)-L-glutamate for imaging of xC transporter activity in hepatocellular carcinoma using PET: preclinical and exploratory clinical studies. J Nucl Med. 2013 Jan;54(1):117-23. doi: 10.2967/jnumed.112.108704. Epub 2012 Dec 11.
- 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.
Dae Hyuk Moon, MD principal investigator
Asan Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing [18F]FSPG in people with Graft Rejection and Heart Transplantation, run by Asan Medical Center at 1 site in South Korea.
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 3 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: finished, as of the sponsor's last update on 20 Jul 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 South Korea. 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.
What does this phase mean?
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?
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?
Sensitivity and specificity of qualitative [18F]FSPG PET/CT interpretation for the diagnosis of patients with histologic evidence of acute allograft rejection (time frame: within 7 days of [18F]FSPG PET/CT). 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 NCT04488094, which also lists 4 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 20 Jul 2023.