Glutamine PET Imaging in LAM

Sponsor

Vanderbilt University Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT04388371

Collaborator

The LAM Foundation (Other)

Enrollment

Location

Arms

21.7

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In this study, subjects with spontaneous or tuberous sclerosis complex associated lymphangioleiomyomatosis (LAM) who have not been started on therapy with mTOR inhibitors such as sirolimus or everolimus to undergo a PET/CT scan using an novel PET tracer that may better evaluate disease activity in LAM subjects both before and after the initiation of mTOR inhibitor therapy will be enrolled. The procedure for each scan will be similar, involving one administration of the novel tracer C11-glutamine followed by a whole body PET/CT scan.

Condition or Disease	Intervention/Treatment	Phase
Lymphangioleiomyomatosis (LAM)	Drug: Glutamine	Phase 1

Detailed Description

Objectives This is a hypothesis-driven prospective pilot study of the targeted PET reagent 11C-Glutamine in LAM.

The objective is to test the hypothesis that 11C-Glutamine PET/CT will demonstrate uptake within the lungs and/or associated neoplasm of patients with LAM and that this effect will be modified by treatment with mTOR inhibitors.

Rationale Our rationale is that 11C-Glutamine PET/CT may provide an improved ability to diagnose LAM, as well as predict and monitor treatment response to mTOR inhibitors.

Aims Test the hypothesis that 11C-Gln PET imaging of the lungs in humans will reflect the known "glutamine addiction" seen in mechanistic preclinical studies of LAM. As a result, PET imaging will show increased tracer uptake in affected areas of diseased lungs and will show reduced uptake after initiating treatment with mTOR inhibitors.

Approach: We will evaluate 11C-Glutamine PET/CT uptake in patients with known LAM, and if possible, we will test subjects again after 8 weeks of mTOR inhibitor therapy (either sirolimus or everolimus).

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Test subjects with spontaneous or tuberous sclerosis complex associated lymphangioleiomyomatosis (LAM) who have not been started on therapy with mTOR inhibitors such as sirolimus or everolimus to undergo a PET/CT scan using an novel PET tracer that may better evaluate disease activity in LAM subjects both before and after the initiation of mTOR inhibitor therapy.Test subjects with spontaneous or tuberous sclerosis complex associated lymphangioleiomyomatosis (LAM) who have not been started on therapy with mTOR inhibitors such as sirolimus or everolimus to undergo a PET/CT scan using an novel PET tracer that may better evaluate disease activity in LAM subjects both before and after the initiation of mTOR inhibitor therapy.

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Glutamine PET Imaging in LAM

Actual Study Start Date :

Oct 18, 2019

Actual Primary Completion Date :

Jun 30, 2021

Actual Study Completion Date :

Aug 10, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prior to subject taking sirolimus or everolimus To compare images from subjects prior to use of sirolimus or everolimus to images produced after use of sirolimus or everolimus.	Drug: Glutamine Glutamine will be administered by IV injection prior to PET imaging.
Experimental: subjects taking sirolimus or everolimus To compare images from subjects prior to use of sirolimus or everolimus to images produced after use of sirolimus or everolimus.	Drug: Glutamine Glutamine will be administered by IV injection prior to PET imaging.

Arm

Intervention/Treatment

Experimental: Prior to subject taking sirolimus or everolimus

To compare images from subjects prior to use of sirolimus or everolimus to images produced after use of sirolimus or everolimus.

Drug: Glutamine

Glutamine will be administered by IV injection prior to PET imaging.

Experimental: subjects taking sirolimus or everolimus

To compare images from subjects prior to use of sirolimus or everolimus to images produced after use of sirolimus or everolimus.

Drug: Glutamine

Glutamine will be administered by IV injection prior to PET imaging.

Outcome Measures

Primary Outcome Measures

Evaluate the uptake of the PET tracer throughout the entire lung and any associated neoplasms (AML, Lymphangiomas) in patients with LAM [8 weeks]
While these imaging techniques have not been used in normal populations, the pulmonary uptake of patients with known intraabdominal malignancy will serve as control for evaluation of any potential uptake. When comparing treatment effects, each patient can serve as their own control as they will have already had imaging completed prior to the initiation of therapy. VEGF-D levels will be collected from clinical laboratory assessment or will be collected at time of enrollment, and relative elevation of VEGF-D will be compared to the relative uptake of tracer within the pulmonary parenchyma of each individual patient.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Female subjects
≥ 18 years of age
Diagnosis of LAM via either a. Histopathologic diagnosis b. Compatible CT chest and one of the following i. Tuberous Sclerosis Complex* ii. Angiomyolipoma or lymphangioma

Chylous Effusion iv. Serum VEGF-D level >800 pg/mL

The diagnosis of TSC will be based on the presence of at least two major criteria or one major and one or more minor features per published guidelines.(30)

Exclusion Criteria:

Patients with any known intrathoracic cancer (primary lung cancer or metastatic disease) or undergoing active treatment for malignancy
Patients with use of investigational therapies for LAM either currently or in the prior 3 months
Patients with body weight ≥400 pounds or body habitus or disability that will not permit the imaging protocol to be performed
Patients known to be pregnant or breastfeeding
Patients with clinically active known or suspected pulmonary infection of any type
Patients known or suspected to have any inborn error of metabolism
Patients with known type I diabetes mellitus
Patients who cannot have a peripheral IV for any reason
Patients who cannot lie flat for the duration of the PET scan
Patients who are claustrophobic
Patients with a prior allergy to contrast agents or to PET tracers

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

Vanderbilt University Medical Center
The LAM Foundation

Investigators

Principal Investigator: Timothy S Blackwell, MD, Vanderbilt University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Timothy Blackwell, Principal Investigator, Vanderbilt University Medical Center

ClinicalTrials.gov Identifier:

NCT04388371

Other Study ID Numbers:

190481

First Posted:

May 14, 2020

Last Update Posted:

Aug 11, 2021

Last Verified:

Aug 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Lymphangioleiomyomatosis

Study Results

No Results Posted as of Aug 11, 2021