Parkinson DiseasePhase 1CLINDENCT00612872
Evaluation of [123I]CLINDE and SPECT as a Marker of Inflammation in Subjects With PD or AD and in Healthy Subjects
A Phase 1 study testing [123I]CLINDE in people with Parkinson Disease and Alzheimer Disease, run by Institute for Neurodegenerative Disorders at 1 site in United States.
Trial summary
To assess the dynamic uptake and washout of 123-I CLINDE, a potential imaging biomarker for inflammatory changes in brain, using single photon emission computed tomography (SPECT) in similarly aged healthy controls and subjects with Alzheimer (AD) or Parkinson disease (PD). Read more about this study
- Who is it for?
- Ages 30 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Parkinson Disease, Alzheimer Disease, Healthy Controls
- What is being tested?
- [123I]CLINDE
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2008to 1 Nov 2009
- 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 30 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Alzheimer's Subject Selection. Subjects who have a clinical diagnosis of mild to moderate Alzheimer's disease will be recruited for this study. The following criteria will be met for inclusion of AD subjects in this study:
- The participant is 50 years or older.
- Written informed consent is obtained.
- Participants have a clinical diagnosis of probable Alzheimer's disease based on National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria.
- Mini-Mental Status Exam score < 25.
- Modified Hachinski Ischemia Scale score of ≤ 4.
Show all 21Show fewer
- Geriatric Depression Scales (GDS) ≤ 10.
- For females, non-child bearing potential a negative urine or blood pregnancy test on day of 123-I CLINDE injection.
- Parkinson's Subject Selection. Subjects who have a clinical diagnosis of mild to moderate Parkinson disease will be recruited for this study. The following criteria will be met for inclusion of PD subjects in this study:
- The participant is 30 years or older.
- Written informed consent is obtained.
- Participants have a clinical diagnosis of Parkinson disease (at least two of the three cardinal symptoms: resting tremor, rigidity, bradykinesia).
- Geriatric Depression Scales (GDS) ≤ 10.
- Hoehn and Yahr ≤4.
- For females, non-child bearing potential a negative urine or blood pregnancy test on day of 123-I CLINDE injection.
- Healthy Control Subject Selection. Healthy control subjects who have no neurological disease will be recruited for this study. The following criteria will be met for inclusion of healthy control subjects in this study:
- The participant is 30 years or older.
- Written informed consent is obtained.
- Negative history of neurological or psychiatric illness based on evaluation by a research physician.
- Mini-Mental Status Exam score ≥28.
- For females, non-child bearing potential a negative urine or blood pregnancy test on day of 123-I CLINDE injection.
Who cannot join
- Alzheimer's subjects will be excluded from participation for the following reasons:
- The subject has a history of significant cerebrovascular disease.
- The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness
- The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
- Pregnancy
- Positive urine drug test.
Show all 16Show fewer
- Parkinson's subjects will be excluded from participation for the following reasons:
- The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness
- The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
- Pregnancy
- Positive urine drug test.
- Healthy control subjects will be excluded from participation for the following reasons:
- The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness.
- The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
- Pregnancy
- Positive urine drug test.
Trial locations and contacts
1 site in 1 country.
United States1 site
Institute for Neurodegenerative Disorders
New Haven, Connecticut, 06510
About this study
Official title: Evaluation of [123I]CLINDE and SPECT as a Marker of Inflammation in Subjects With Parkinson Disease or Alzheimer Disease and in Healthy Subjects
To assess the dynamic uptake and washout of 123-I CLINDE, a potential imaging biomarker for inflammatory changes in brain, using single photon emission computed tomography (SPECT) in similarly aged healthy controls and subjects with Alzheimer (AD) or Parkinson disease (PD).
To perform blood metabolite characterization of 123-I CLINDE in healthy and subjects with AD or PD to determine the nature of metabolites in assessment of 123-I CLINDE as a single photon computed tomography (SPECT) brain imaging agent.
Evaluate the test/retest reproducibility of 123-I CLINDE, and SPECT in AD and PD subjects and healthy controls
Read the detailed description
When microglia become activated they express peripheral benzodiazepine receptors (PBR) or binding sites on their mitochondrial membrane. PBRs are functionally and structurally distinct from central benzodiazepine receptors associated with y-aminiobutric acid (GABA)-regulated chloride channels. PBRs are found in abundance in peripheral organs and hematologic cells, but are present at only very low levels in the normal central nervous system (Banati, 2002). CLINDE is a phenylimidazopyridine and appears to bind selectively to the PBR. In the absence of excessive blood in the CNS an increase CLINDE binding to PBR is a potential marker of microglial activation in the CNS. The increase in CLINDE binding may be an indicator of the transition of microglia from a resting to an activated state. When labeled with 123-I and used as a SPECT radiotracer, CLINDE may serve as an in vivo marker of microglial activation in Alzheimer disease and Parkinson disease.
The 123-I radioactive tag offers distinct advantages for large-scale clinical imaging studies of anti-inflammatory targeted treatments as a marker of microglial activation and efficacy of therapeutic intervention. The half-life (13.1 h) of 123-I permits imaging in multiple subjects in a single research-dedicated imaging center, with multiple research subjects per day. This minimizes variability introduced in multi-center quantitative imaging trials where different cameras, image processing methods, and QA procedures all conspire to increase the variance imaging biomarkers. Using this model, our group pioneered a method to evaluate the loss of dopamine function in Parkinson's disease using a radioactive drug 123-I β-CIT which binds directly to dopamine nerve terminals.
The adaptation of imaging agents like 123-I CLINDE as a biomarker of microglial activation in neurodegenerative diseases requires human validation studies. Expanding upon our previous work with b-amyloid ligands (123I-IMPY, 123-I MNI-187) for AD and dopamine transporter ligands (123-I B-CIT, Altropane) for PD, we desire to develop and characterize 123-I CLINDE as a potential marker for microglial activation in association with neuronal damage that may be applicable to multiple neurodegenerative diseases. Ultimately a marker of microglial activation could be used for large-scale quantitative brain imaging trials in AD or PD, specifically to investigate the agent as an objective biomarker in treatments aimed at reducing inflammatory changes in these conditions. The significance of this work lies in applying state-of-art quantitative neuroimaging tools to develop a relevant biomarker in individuals with neurodegenerative diseases with the intention of using this efficiently in large clinical imaging trials.
- Being tested
- [123I]CLINDE
- Medical subject headings
- Parkinson Disease, Alzheimer Disease, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[123I]CLINDEDrug
Subjects will be injected with up to 5 mCi and not to exceed 5.5 (not >10% of 5 mCi limit) of 123-I CLINDE followed by serial SPECT imaging.
| Study group | Role | What they receive |
|---|---|---|
| Assess [123-I]CLINDE and brain imaging | Experimental | Subjects will be injected with up to 5 mCi and not to exceed 5.5 (not >10% of 5 mCi limit) of 123-I CLINDE followed by serial SPECT imaging. Receives: Drug: [123I]CLINDE |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the dynamic uptake and washout of 123-I CLINDE, using single photon emission computed tomography (SPECT) in similarly aged healthy controls and subjects with Alzheimer (AD) or Parkinson disease (PD).
Measured: 6 mos
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2008 (estimated)
- Study startJan 2008
- Primary completion1 Nov 2009
- Study completion1 Nov 2009
Why it stopped: Results did not show reason to continue with study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies 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
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute for Neurodegenerative Disorders
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Danna L Jennings, M.D., Principal investigator, Institute for Neurodegenerative Disorders
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00612872
- Sponsor's protocol ID
- CLINDE 001
- Other IDs
- IND 100,863
- Acronym
- CLINDE
- Status last verified
- Apr 2019
- First submitted
- 16 Jan 2008
- Last updated
- 3 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Aktas O, Ullrich O, Infante-Duarte C, Nitsch R, Zipp F. Neuronal damage in brain inflammation. Arch Neurol. 2007 Feb;64(2):185-9. doi: 10.1001/archneur.64.2.185.
PubMed 17296833Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection. Report of a Working Group of the American Academy of Neurology AIDS Task Force. Neurology. 1991 Jun;41(6):778-85. doi: 10.1212/wnl.41.6.778. No abstract available.
PubMed 2046917
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of [123I]CLINDE and SPECT as a Marker of Inflammation in Subjects With Parkinson Disease or Alzheimer Disease and in Healthy Subjects
- ClinicalTrials.gov ID
- NCT00612872
- Acronym / sponsor ID
- CLINDE / CLINDE 001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Results did not show reason to continue with study.
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Institute for Neurodegenerative DisordersUniversity, hospital or other
- Study start
- Jan 2008
- Primary completion
- 1 Nov 2009 (actual)
- Study completion
- 1 Nov 2009 (actual)
- First posted
- 12 Feb 2008 (estimated)
- 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.
To assess the dynamic uptake and washout of 123-I CLINDE, a potential imaging biomarker for inflammatory changes in brain, using single photon emission computed tomography (SPECT) in similarly aged healthy controls and subjects with Alzheimer (AD) or Parkinson disease (PD).
To perform blood metabolite characterization of 123-I CLINDE in healthy and subjects with AD or PD to determine the nature of metabolites in assessment of 123-I CLINDE as a single photon computed tomography (SPECT) brain imaging agent.
Evaluate the test/retest reproducibility of 123-I CLINDE, and SPECT in AD and PD subjects and healthy controls
Detailed description
When microglia become activated they express peripheral benzodiazepine receptors (PBR) or binding sites on their mitochondrial membrane. PBRs are functionally and structurally distinct from central benzodiazepine receptors associated with y-aminiobutric acid (GABA)-regulated chloride channels. PBRs are found in abundance in peripheral organs and hematologic cells, but are present at only very low levels in the normal central nervous system (Banati, 2002). CLINDE is a phenylimidazopyridine and appears to bind selectively to the PBR. In the absence of excessive blood in the CNS an increase CLINDE binding to PBR is a potential marker of microglial activation in the CNS. The increase in CLINDE binding may be an indicator of the transition of microglia from a resting to an activated state. When labeled with 123-I and used as a SPECT radiotracer, CLINDE may serve as an in vivo marker of microglial activation in Alzheimer disease and Parkinson disease.
The 123-I radioactive tag offers distinct advantages for large-scale clinical imaging studies of anti-inflammatory targeted treatments as a marker of microglial activation and efficacy of therapeutic intervention. The half-life (13.1 h) of 123-I permits imaging in multiple subjects in a single research-dedicated imaging center, with multiple research subjects per day. This minimizes variability introduced in multi-center quantitative imaging trials where different cameras, image processing methods, and QA procedures all conspire to increase the variance imaging biomarkers. Using this model, our group pioneered a method to evaluate the loss of dopamine function in Parkinson's disease using a radioactive drug 123-I β-CIT which binds directly to dopamine nerve terminals.
The adaptation of imaging agents like 123-I CLINDE as a biomarker of microglial activation in neurodegenerative diseases requires human validation studies. Expanding upon our previous work with b-amyloid ligands (123I-IMPY, 123-I MNI-187) for AD and dopamine transporter ligands (123-I B-CIT, Altropane) for PD, we desire to develop and characterize 123-I CLINDE as a potential marker for microglial activation in association with neuronal damage that may be applicable to multiple neurodegenerative diseases. Ultimately a marker of microglial activation could be used for large-scale quantitative brain imaging trials in AD or PD, specifically to investigate the agent as an objective biomarker in treatments aimed at reducing inflammatory changes in these conditions. The significance of this work lies in applying state-of-art quantitative neuroimaging tools to develop a relevant biomarker in individuals with neurodegenerative diseases with the intention of using this efficiently in large clinical imaging trials.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Assess [123-I]CLINDE and brain imaging | Experimental | Drug: [123I]CLINDESubjects will be injected with up to 5 mCi and not to exceed 5.5 (not >10% of 5 mCi limit) of 123-I CLINDE followed by serial SPECT imaging. |
Who may qualify
- Ages
- 30 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (21 listed)
- Alzheimer's Subject Selection. Subjects who have a clinical diagnosis of mild to moderate Alzheimer's disease will be recruited for this study. The following criteria will be met for inclusion of AD subjects in this study:
- The participant is 50 years or older.
- Written informed consent is obtained.
- Participants have a clinical diagnosis of probable Alzheimer's disease based on National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria.
- Mini-Mental Status Exam score < 25.
Key exclusion criteria (16 listed)
- The subject has a history of significant cerebrovascular disease.
- The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness
- The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
- Pregnancy
- Positive urine drug test.
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 |
|---|---|---|
| [123I]CLINDESubjects will be injected with up to 5 mCi and not to exceed 5.5 (not >10% of 5 mCi limit) of 123-I CLINDE followed by serial SPECT imaging. | Drug | Assess [123-I]CLINDE and brain imaging |
Primary outcome
To assess the dynamic uptake and washout of 123-I CLINDE, using single photon emission computed tomography (SPECT) in similarly aged healthy controls and subjects with Alzheimer (AD) or Parkinson disease (PD).
Time frame: 6 mos
Results and safety
The study was stopped early (reason given: Results did not show reason to continue with study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2019.
- Background: PubMed 17296833Aktas O, Ullrich O, Infante-Duarte C, Nitsch R, Zipp F. Neuronal damage in brain inflammation. Arch Neurol. 2007 Feb;64(2):185-9. doi: 10.1001/archneur.64.2.185.
- Background: PubMed 2046917Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection. Report of a Working Group of the American Academy of Neurology AIDS Task Force. Neurology. 1991 Jun;41(6):778-85. doi: 10.1212/wnl.41.6.778. No abstract available.
- IND web pageLink provided by the sponsor.
Related trials for Parkinson Disease
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Enrolling by invitationObservational study
Early Molecular Biomarkers for Differentiating Parkinsonian Syndromes
PARKINSON DISEASE (Disorder), Atypical Parkinsonism
RecruitingPhase 3
A Clinical Study of Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) as First-line Maintenance Treatment of Cervical Cancer (MK-2870-036/TroFuse-036/GOG-3123/ENGOT-cx22)
Cervical Cancer
Active, not recruitingPhase 1/2
Clinical Safety and Efficacy of Umbilical Cord Mesenchymal Stromal Cells-derived Exosomes in Patients With Parkinson's Disease
Parkinson Disease (PD)
Active, not recruitingObservational study
Adaptive DBS to Offset STN Dysregulation During Exercise in PD
Parkinson Disease
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.
Danna L Jennings, M.D. principal investigator
Institute for Neurodegenerative Disorders
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing [123I]CLINDE in people with Parkinson Disease and Alzheimer Disease, run by Institute for Neurodegenerative Disorders 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 21 inclusion and 16 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: stopped early, as of the sponsor's last update on 3 Apr 2019. 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. 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 stopped early (reason given: Results did not show reason to continue with study.). Results are not available in the source record.
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?
To assess the dynamic uptake and washout of 123-I CLINDE, using single photon emission computed tomography (SPECT) in similarly aged healthy controls and subjects with Alzheimer (AD) or Parkinson disease (PD). (time frame: 6 mos). 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 NCT00612872, which also lists 2 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 3 Apr 2019.