Feasibility of [11C]Acetate-PET in LAM and TSC

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	Female

More Inclusion & Exclusion 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05467397
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Brigham and Women's Hospital
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Carmen P Priolo, MD PhD
Principal Investigator Affiliation	Brigham and Women's Hospital
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Lymphangioleiomyomatosis, Tuberous Sclerosis Complex

Additional Details

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.

Arms & Interventions

Arms

Experimental: Patients will undergo [11C]acetate PET/CT

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.

Interventions

Drug: - [11C]acetate

Positron Emission Tomography (PET)

Contact a Trial Team

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Brigham and Women's Hospital, Boston, Massachusetts

Status

Recruiting

Address

Brigham and Women's Hospital

Boston, Massachusetts, 02115

Site Contact

Carmen Priolo

[email protected]

857-307-0783

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