Feasibility of [11C]Acetate-PET in LAM and TSC
Primary Purpose
Lymphangioleiomyomatosis, Tuberous Sclerosis Complex
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
[11C]acetate
Sponsored by
About this trial
This is an interventional diagnostic trial for Lymphangioleiomyomatosis
Eligibility Criteria
Inclusion Criteria:
- diagnosis of LAM (or TSC-LAM)
- age 18 or over
- at least one renal angiomyolipoma (at least 1 cm in each diameter) confirmed by CT or MRI
- no prior treatment with rapamycin/rapalogs OR candidate for initiating treatment with rapamycin/rapalogs OR under treatment with rapamycin/rapalogs for minimum 3 months and maximum of 1 year
Exclusion Criteria:
- under treatment with rapamycin or rapalogs for < 3 months or > 1 year
- participated in research studies involving radiation exposure (> 50 mSv/year) in the past 12 months
Sites / Locations
- Brigham and Women's HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Patients will undergo [11C]acetate PET/CT
Arm Description
Patients will undergo a single [11c]acetate PET scan OR Patients will undergo an [11c]acetate PET scan, initiate treatment with rapamycin or rapalogs and receive a second [11c]acetate PET scan 3 or 4 months after starting the treatment.
Outcomes
Primary Outcome Measures
Quantitative analysis of [11C]acetate uptake in renal angiomyolipoma and pulmonary LAM
Standardized uptake value (SUV) will be used to quantify uptake
Secondary Outcome Measures
Feasibility of [11C]acetate PET as a biomarker of mTORC1 inhibition in LAM/TSC proliferative lesions
Standardized uptake value (SUV) will be used to quantify uptake
Full Information
NCT ID
NCT05467397
First Posted
July 18, 2022
Last Updated
July 28, 2023
Sponsor
Brigham and Women's Hospital
Collaborators
Massachusetts General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05467397
Brief Title
Feasibility of [11C]Acetate-PET in LAM and TSC
Official Title
Feasibility Study of [11C]Acetate Positron Emission Tomography (PET) as an Indicator of Early Response to Rapamycin in Lymphangioleiomyomatosis (LAM) Patients
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 30, 2021 (Actual)
Primary Completion Date
August 30, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
Massachusetts General Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study aims to assess [11C]acetate positron emission tomography (PET)/computed tomography (CT) as a biomarker for renal angiomyolipomas and pulmonary lymphangioleiomyomatosis (LAM) and an early biomarker of response to rapamycin in LAM patients.
[11C]Acetate is a radioactive form of acetate, a nutrient commonly processed in our body's cells to generate fat and energy. Preclinical studies support the hypothesis that TSC tumors enhance lipid synthesis compared to normal tissues, suggesting that quantification of [11C]acetate in these tumors by PET/CT may provide a metabolic biomarker of disease.
Participants in the study will undergo 1 or 2 PET/CT scans over 3 to 6 months at the Massachusetts General Hospital (Boston, MA). [11C]acetate is administered through an intravenous catheter. This small amount of radioactivity is short-lived and eliminated from the body within a few hours.
Detailed Description
Lymphangioleiomyomatosis (LAM) is a rare, multisystem disease of women, consisting of a diffuse proliferation of smooth muscle actin-positive cells (LAM cells), which harbor inactivating mutations in either the TSC1 or TSC2 tumor suppressor gene. These inactivating mutations result in constitutive activation of mammalian/mechanistic TOR (target of rapamycin) complex 1 (mTORC1), which integrates growth factor and nutrient signaling to stimulate cell growth and metabolism. Pulmonary LAM is characterized by associated progressive cystic destruction of the lung parenchyma, recurrent pneumothorax, and chylous pleural effusions. Extrapulmonary proliferative lesions of LAM include renal angiomyolipomas and lymphangiomyomas. LAM can occur as a sporadic disorder where LAM cells harbor somatic inactivating mutations of the TSC1 or TSC2 gene, or in women with Tuberous Sclerosis Complex (TSC).
Rapamycin is an FKBP12-dependent allosteric inhibitor of mTORC1 approved by the FDA for the treatment of LAM and TSC-associated renal angiomyolipomas. Clinical trials of TSC and LAM have shown that 12 month-treatment with rapamycin induces response of renal angiomyolipomas and stabilization of pulmonary function. However, lung function decline and tumor growth resume when treatment is interrupted.
Sensitive and specific biomarkers of response to therapy and/or disease progression, including biomarkers of tumor metabolic activity, would facilitate clinical trials of novel therapeutic agents for LAM and enable optimization of current rapamycin-based regimens.
Our preclinical studies showed that lipogenic pathways can be detected in preclinical animal models of TSC and LAM using PET-based metabolic imaging.
The proposed study aims to quantitatively and non-invasively assess metabolic activity and response to rapamycin in LAM patients using [11C]acetate positron emission tomography (PET) imaging.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphangioleiomyomatosis, Tuberous Sclerosis Complex
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Patients will undergo [11C]acetate PET/CT
Arm Type
Experimental
Arm Description
Patients will undergo a single [11c]acetate PET scan OR Patients will undergo an [11c]acetate PET scan, initiate treatment with rapamycin or rapalogs and receive a second [11c]acetate PET scan 3 or 4 months after starting the treatment.
Intervention Type
Drug
Intervention Name(s)
[11C]acetate
Other Intervention Name(s)
diagnostic test
Intervention Description
Positron Emission Tomography (PET)
Primary Outcome Measure Information:
Title
Quantitative analysis of [11C]acetate uptake in renal angiomyolipoma and pulmonary LAM
Description
Standardized uptake value (SUV) will be used to quantify uptake
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Feasibility of [11C]acetate PET as a biomarker of mTORC1 inhibition in LAM/TSC proliferative lesions
Description
Standardized uptake value (SUV) will be used to quantify uptake
Time Frame
4 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
diagnosis of LAM (or TSC-LAM)
age 18 or over
at least one renal angiomyolipoma (at least 1 cm in each diameter) confirmed by CT or MRI
no prior treatment with rapamycin/rapalogs OR candidate for initiating treatment with rapamycin/rapalogs OR under treatment with rapamycin/rapalogs for minimum 3 months and maximum of 1 year
Exclusion Criteria:
under treatment with rapamycin or rapalogs for < 3 months or > 1 year
participated in research studies involving radiation exposure (> 50 mSv/year) in the past 12 months
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Carmen Priolo
Phone
8573070783
Email
cpriolo@partners.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carmen P Priolo, MD PhD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carmen Priolo
Phone
857-307-0783
Email
cpriolo@partners.org
12. IPD Sharing Statement
Learn more about this trial
Feasibility of [11C]Acetate-PET in LAM and TSC
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