Healthy VolunteersEarly Phase 1NCT02236754
Evaluation of 18 F-FP-DTBZ Pancreatic PET Scanning as a Tool to Measure Beta Cell Mass
A Early Phase 1 study testing 18 F-FP-DTBZ and PET Scanning in people with Healthy Volunteers and Diabetes Mellitus, Type 1, run by Columbia University at 1 site in United States.
Trial summary
Type 1 diabetes mellitus (T1DM) develops when there is impaired insulin production due to loss of insulin producing cells (beta cells). The amount of insulin that can be produced is imperfectly correlated with beta cell mass (BCM). Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers, Diabetes Mellitus, Type 1
- What is being tested?
- 18 F-FP-DTBZ and PET Scanning
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jul 2013to 23 Apr 2014
- 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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients with type 1 diabetes may be enrolled if they meet all of the following criteria:
- Are males or females between 18 and 70 years of age, inclusive
- Have a diagnosis of type 1 diabetes mellitus as defined by the American Diabetes Association (ADA) criteria or by diagnosed as per their endocrinologist; duration >5 years; Insulin dose requirements <0.8 units/kg/day
- HbA1c level between 5% and 8.5%
- Have fasting C-Peptide < 0.1 ng/ml
- Have a body mass index (BMI) between 18 and 32 kg/m2
Show all 19Show fewer
- Able to tolerate PET imaging
- In the judgment of the physician, are capable of fasting 4 to 6 hours prior to screening and Day 1 imaging procedures
- Give informed consent
- Healthy volunteers may be enrolled if they meeting all of the following criteria:
- Are males or females between 18 and 70 years of age, inclusive
- Have no history of type 1 or type 2 diabetes in a first degree relative
- Fasting blood glucose less than 100 mg/dL
- HbA1c level less than 6%
- Normal Mixed Meal Tolerance test at screening visit
- BMI between 18 and 32 kg/m2
- Able to tolerate PET imaging
- In the judgment of the physician, are capable of fasting 4 to 6 hours prior to screening and Day 1 imaging procedures, and
- Give informed consent
Who cannot join
- Potential participants must not have any of the following exclusion criteria:
- Clinically significant renal dysfunction
- Clinically significant liver dysfunction as determined by history, physical examination, and standard liver function testing at screening (aspartate aminotransferase (AST), alanine aminotransferase (ALT), Total/Direct Bilirubin, Alkaline Phosphatase)
- Coagulopathy
- Use medications known to affect dopaminergic function, including monoamine oxidase (MAO) inhibitors, tetrabenazine, or levodopa
- Recent (within 3 months) or current treatment with drugs influencing beta cell function or insulin sensitivity (e.g. glucocorticoids, reserpine) medications known to affect dopaminergic function, including MAO inhibitors, tetrabenazine, or levodopa
Show all 20Show fewer
- Have polycystic ovarian syndrome
- History of movement disorder such as Parkinson's Disease, Huntington's Disease
- Clinically significant psychiatric disease or history of psychiatric illness such as depression, bipolar disease, anxiety or schizophrenia
- Current use (within past year) of cocaine, methamphetamine, and/or ecstasy (3,4methylenedioxymethamphetamine (MDMA))
- Have a recent history of alcohol or substance abuse or dependence
- Clinically significant cardiovascular disease or clinically significant abnormalities on screening electrocardiogram (ECG) (including but not limited to QT-interval time corrected > 450 msec)
- Clinically significant pulmonary, renal or hepatic impairment, or cancer
- Have clinically significant infectious disease, including acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV) infection or previous positive test for hepatitis B, hepatitis C, or HIV.
- Are women of childbearing potential not refraining from sexual activity or not using adequate contraception.
- Women must not be pregnant (negative serum human chorionic gonadotropin (hCG) at the time of screen) or breastfeeding at screening, and must agree to take appropriate steps not to become pregnant during for 30 days following the clinical trial
- Require medications with a narrow therapeutic window (e.g., warfarin), are receiving any investigational medications, or have participated in a trial with investigational medications within the last 30 days
- Weigh more than the manufacturer recommended limit for the PET/computed tomography (CT) camera being used
- Any prior participation in other research protocols within the past month that involved radiation, with the exception of plain radiography studies (i.e., chest x-rays); And
- Have received a diagnostic or therapeutic radiopharmaceutical within the past week
Trial locations and contacts
1 site in 1 country.
United States1 site
Naomi Berrie Diabetes Center
New York, New York, 10032
About this study
Official title: Scan Re-Scan Pancreatic Beta Cell Imaging Using PET Imaging and 18 F-FP-DTBZ
Type 1 diabetes mellitus (T1DM) develops when there is impaired insulin production due to loss of insulin producing cells (beta cells). The amount of insulin that can be produced is imperfectly correlated with beta cell mass (BCM). The development of a reliable method to noninvasively quantify the total amount of insulin producing beta cells would be of great benefit by providing an important endpoint for the development of new treatments of diabetes. The investigators have previously identified a specific marker on islet cells called vesicular monoamine transporter 2 (VMAT2) that the investigators now propose to use in positron emission tomography (PET) scanning to determine islet beta cell mass. The PET radiopharmaceutical 18 F-fluoropropyl(FP)-dihydrotetrabenazine(DTBZ) has been used previously in human subjects without adverse effects. It has shown promise in differentiating type 1 diabetes and non-diabetes. The investigators now hypothesize that repeat PET scans will be reproducible in the same subject. Subjects with normal BCM will be recruited from among normal weight non-diabetic people with plasma insulin levels within the normal range. Subjects with predicted reduced BCM will be recruited from among patients with T1DM who have low or non-measurable insulin levels. Two PET scan measurements will be taken in each subject and the amount of VMAT2 in the pancreas will be and compared for reproducible findings. Biochemical testing will also be performed and compared to PET scans as a potential indirect marker of beta cell mass.
Read the detailed description
Diabetes results when the insulin secretory capacity of the beta cell population is lost or severely compromised.Plasma insulin levels have been used as a surrogate marker of beta cell mass (BCM) but insulin levels often do not correlate well. A "gold standard of measurement" to obtain BCM would be of great value. The aim of the proposed study is to evaluate an islet imaging technique using PET scanning to directly measure BCM and thus provide valuable information for monitoring disease progress and response to therapy in people with diabetes and in people at high risk for diabetes. Type 1 diabetes (T1DM) occurs when the beta cells are selectively destroyed by a T cell mediated autoimmune process. People at high risk for developing T1DM, such as first degree relatives of patients with T1DM, can sometimes be identified before the disease develops by measuring autoantibodies to beta cells, however this test is neither sensitive nor specific. Little is known about the natural history of BCM, turnover and cell lifetime, or the course of inflammation in diabetes. This is principally because the pancreas is a highly heterogeneous organ that is difficult to biopsy without significant complications, and BCM only comprises 1 to 2% of the total volume. Accurate assessment of BCM in human diabetes is limited to autopsy studies, which usually suffer from inadequate clinical information; thus, the development of non-invasive means of BCM measurement could be important for interventional therapies of T1DM, islet regeneration/stem cell therapy and islet transplantation.
- Conditions
- Healthy Volunteers, Diabetes Mellitus, Type 1
- Being tested
- 18 F-FP-DTBZ, PET Scanning
- Keywords
- dihydrotetrabenazine, beta cell mass, diabetes mellitus
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
18 F-FP-DTBZDrug
The drug, no carrier added [18 F]-FP-DTBZ, is formulated in 5% (v/v) ethanol in 0.9% sterile saline solution to produce [18 F]-FP-DTBZ for injection. Subjects will receive a single i.v. administration of no more than 7.6 millicuries (mCi) of [18 F]-FP-DTBZ for injection immediately prior to imaging. The specific activity at time of injection will less than 1.0 mCi/microgram and thus for a 7.6 mCi dose the maximal mass dose will be less than 10 microgram.
PET ScanningRadiation
Also called Positron Emission Tomography
Individuals will be imaged continuously (i.e. dynamically) for 2 hours.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Controls | Other | Pancreatic 18 F-FP-DTBZ uptake will be measured with PET scanning in healthy controls: subjects with predicted normal BCM (healthy, normal weight, non-diabetic individuals who have stimulated insulin and c-peptide levels within the normal range). Receives: Drug: 18 F-FP-DTBZ; Radiation: PET Scanning |
| Patients with T1D | Other | Pancreatic 18 F-FP-DTBZ uptake will be measured with PET scanning in patients with longstanding T1D: subjects with predicted reduced beta cell mass (subjects with established T1DM who have low or no measurable stimulated insulin and c-peptide levels). Receives: Drug: 18 F-FP-DTBZ; Radiation: PET Scanning |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean VMAT2 Functional Binding Capacity in the β Cells to 18 F-FP-DTBZ
The VMAT2 functional binding capacity in the body and tail of the pancreas is calculated as BPND (VMAT2 binding potential) × PET ROI (region-of-interest) Volume. BPND is unitless, and ROI unit is mL. Higher values of the VMAT functional binding capacity indicates greater β cell mass.
Measured: Up to 2 months from enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2014 (estimated)
- Study start2 Jul 2013
- Primary completion23 Apr 2014
- Study completion23 Apr 2014
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 (2)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul Harris, PhD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02236754
- Sponsor's protocol ID
- AAAJ5709
- Other IDs
- R01DK077493-03
- Status last verified
- Jul 2024
- First submitted
- 28 Jan 2014
- Last updated
- 23 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Goland R, Freeby M, Parsey R, Saisho Y, Kumar D, Simpson N, Hirsch J, Prince M, Maffei A, Mann JJ, Butler PC, Van Heertum R, Leibel RL, Ichise M, Harris PE. 11C-dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls. J Nucl Med. 2009 Mar;50(3):382-9. doi: 10.2967/jnumed.108.054866. Epub 2009 Feb 17.
PubMed 19223416Freeby MJ, Kringas P, Goland RS, Leibel RL, Maffei A, Divgi C, Ichise M, Harris PE. Cross-sectional and Test-Retest Characterization of PET with [(18)F]FP-(+)-DTBZ for beta Cell Mass Estimates in Diabetes. Mol Imaging Biol. 2016 Apr;18(2):292-301. doi: 10.1007/s11307-015-0888-7. Epub 2015 Sep 14.
PubMed 26370678
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Scan Re-Scan Pancreatic Beta Cell Imaging Using PET Imaging and 18 F-FP-DTBZ
- ClinicalTrials.gov ID
- NCT02236754
- Acronym / sponsor ID
- AAAJ5709
- Conditions
- Healthy Volunteers, Diabetes Mellitus, Type 1
- Keywords
- dihydrotetrabenazine, beta cell mass, diabetes mellitus
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 2 Jul 2013 (actual)
- Primary completion
- 23 Apr 2014 (actual)
- Study completion
- 23 Apr 2014 (actual)
- First posted
- 11 Sep 2014 (estimated)
- Results
- Posted 23 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Type 1 diabetes mellitus (T1DM) develops when there is impaired insulin production due to loss of insulin producing cells (beta cells). The amount of insulin that can be produced is imperfectly correlated with beta cell mass (BCM). The development of a reliable method to noninvasively quantify the total amount of insulin producing beta cells would be of great benefit by providing an important endpoint for the development of new treatments of diabetes. The investigators have previously identified a specific marker on islet cells called vesicular monoamine transporter 2 (VMAT2) that the investigators now propose to use in positron emission tomography (PET) scanning to determine islet beta cell mass. The PET radiopharmaceutical 18 F-fluoropropyl(FP)-dihydrotetrabenazine(DTBZ) has been used previously in human subjects without adverse effects. It has shown promise in differentiating type 1 diabetes and non-diabetes. The investigators now hypothesize that repeat PET scans will be reproducible in the same subject. Subjects with normal BCM will be recruited from among normal weight non-diabetic people with plasma insulin levels within the normal range. Subjects with predicted reduced BCM will be recruited from among patients with T1DM who have low or non-measurable insulin levels. Two PET scan measurements will be taken in each subject and the amount of VMAT2 in the pancreas will be and compared for reproducible findings. Biochemical testing will also be performed and compared to PET scans as a potential indirect marker of beta cell mass.
Detailed description
Diabetes results when the insulin secretory capacity of the beta cell population is lost or severely compromised.Plasma insulin levels have been used as a surrogate marker of beta cell mass (BCM) but insulin levels often do not correlate well. A "gold standard of measurement" to obtain BCM would be of great value. The aim of the proposed study is to evaluate an islet imaging technique using PET scanning to directly measure BCM and thus provide valuable information for monitoring disease progress and response to therapy in people with diabetes and in people at high risk for diabetes. Type 1 diabetes (T1DM) occurs when the beta cells are selectively destroyed by a T cell mediated autoimmune process. People at high risk for developing T1DM, such as first degree relatives of patients with T1DM, can sometimes be identified before the disease develops by measuring autoantibodies to beta cells, however this test is neither sensitive nor specific. Little is known about the natural history of BCM, turnover and cell lifetime, or the course of inflammation in diabetes. This is principally because the pancreas is a highly heterogeneous organ that is difficult to biopsy without significant complications, and BCM only comprises 1 to 2% of the total volume. Accurate assessment of BCM in human diabetes is limited to autopsy studies, which usually suffer from inadequate clinical information; thus, the development of non-invasive means of BCM measurement could be important for interventional therapies of T1DM, islet regeneration/stem cell therapy and islet transplantation.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy Controls | Other | Drug: 18 F-FP-DTBZ, Radiation: PET ScanningPancreatic 18 F-FP-DTBZ uptake will be measured with PET scanning in healthy controls: subjects with predicted normal BCM (healthy, normal weight, non-diabetic individuals who have stimulated insulin and c-peptide levels within the normal range). |
| Patients with T1D | Other | Drug: 18 F-FP-DTBZ, Radiation: PET ScanningPancreatic 18 F-FP-DTBZ uptake will be measured with PET scanning in patients with longstanding T1D: subjects with predicted reduced beta cell mass (subjects with established T1DM who have low or no measurable stimulated insulin and c-peptide levels). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients with type 1 diabetes may be enrolled if they meet all of the following criteria:
- Are males or females between 18 and 70 years of age, inclusive
- Have no history of type 1 or type 2 diabetes in a first degree relative
- Fasting blood glucose less than 100 mg/dL
- HbA1c level less than 6%
Key exclusion criteria (20 listed)
- Potential participants must not have any of the following exclusion criteria:
- Women must not be pregnant (negative serum human chorionic gonadotropin (hCG) at the time of screen) or breastfeeding at screening, and must agree to take appropriate steps not to become pregnant during for 30 days following the clinical 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 |
|---|---|---|
| 18 F-FP-DTBZThe drug, no carrier added [18 F]-FP-DTBZ, is formulated in 5% (v/v) ethanol in 0.9% sterile saline solution to produce [18 F]-FP-DTBZ for injection. Subjects will receive a single i.v. administration of no more than 7.6 millicuries (mCi) of [18 F]-FP-DTBZ for injection immediately prior to imaging. The specific activity at time of injection will less than 1.0 mCi/microgram and thus for a 7.6 mCi dose the maximal mass dose will be less than 10 microgram. | Drug | Healthy Controls, Patients with T1D |
| PET ScanningAlso: Positron Emission TomographyIndividuals will be imaged continuously (i.e. dynamically) for 2 hours. | Radiation | Healthy Controls, Patients with T1D |
Primary outcome
Mean VMAT2 Functional Binding Capacity in the β Cells to 18 F-FP-DTBZ
Time frame: Up to 2 months from enrollment
The VMAT2 functional binding capacity in the body and tail of the pancreas is calculated as BPND (VMAT2 binding potential) × PET ROI (region-of-interest) Volume. BPND is unitless, and ROI unit is mL. Higher values of the VMAT functional binding capacity indicates greater β cell mass.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19223416Goland R, Freeby M, Parsey R, Saisho Y, Kumar D, Simpson N, Hirsch J, Prince M, Maffei A, Mann JJ, Butler PC, Van Heertum R, Leibel RL, Ichise M, Harris PE. 11C-dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls. J Nucl Med. 2009 Mar;50(3):382-9. doi: 10.2967/jnumed.108.054866. Epub 2009 Feb 17.
- Results publication: PubMed 26370678Freeby MJ, Kringas P, Goland RS, Leibel RL, Maffei A, Divgi C, Ichise M, Harris PE. Cross-sectional and Test-Retest Characterization of PET with [(18)F]FP-(+)-DTBZ for beta Cell Mass Estimates in Diabetes. Mol Imaging Biol. 2016 Apr;18(2):292-301. doi: 10.1007/s11307-015-0888-7. Epub 2015 Sep 14.
- Investigator web siteLink provided by the sponsor.
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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.
Paul Harris, PhD principal investigator
Columbia University
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 18 F-FP-DTBZ and PET Scanning in people with Healthy Volunteers and Diabetes Mellitus, Type 1, run by Columbia University 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 19 inclusion and 20 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 23 Jul 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. 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 23 Jul 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?
Mean VMAT2 Functional Binding Capacity in the β Cells to 18 F-FP-DTBZ (time frame: Up to 2 months from enrollment). 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 NCT02236754, 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 23 Jul 2024.