Immune Profiling via Thoracic Duct Cannulation for Multiple Sclerosis

Overseen By Margaux Giardino

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Must be taking: Interferons, Glatiramer acetate

Must not be taking: Systemic glucocorticoids

Disqualifiers: Primary progressive MS, Neuromyelitis optica, Active chronic immune disease, Active infections, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores immune cells in people with multiple sclerosis (MS) by collecting lymph fluid through a safe, minimally invasive procedure called thoracic duct cannulation. The study compares immune responses in MS patients to those in healthy individuals, focusing on the impact of an approved MS treatment. Participants may be newly diagnosed or have used specific treatments previously. Ideal candidates have early MS, have been stable for the past month, and have not received recent immune-related treatments. As an unphased trial, this study allows participants to contribute to groundbreaking research that could enhance understanding of MS and improve future treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that participants should not have used systemic glucocorticoids in the past 4 weeks and should have a treatment history limited to Interferons or glatiramer acetate, or be untreated. It's best to discuss your specific medications with the study team.

What prior data suggests that thoracic duct cannulation is safe for immune profiling in multiple sclerosis?

Research shows that thoracic duct cannulation is a minimally invasive procedure, meaning it doesn't involve major surgery and usually carries a lower risk of complications. Studies have found that interventional radiologists, who are doctors trained to use imaging to guide procedures, can perform it safely.

Limited data exists on serious side effects from thoracic duct cannulation itself. However, like any medical procedure, some risks may occur. These could include discomfort at the cannula (a thin tube) insertion site or minor issues like infection, but these are generally manageable.

In summary, while thoracic duct cannulation carries some risks, experienced professionals consider it safe. Always discuss any concerns with your healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the thoracic duct cannulation technique for multiple sclerosis (MS) because it offers a new way to understand the immune system's role in the disease. Unlike standard MS treatments, which often focus on modifying immune responses with medications like interferons or glatiramer acetate, this method directly samples immune cells from the lymphatic system. By using either 'in-and-out' or 'indwelling' catheterization, doctors can get a clearer picture of immune cell activity before and after potential treatments. This could lead to more targeted and effective therapies in the future, as it provides insights that current blood tests can't fully capture.

What evidence suggests that thoracic duct cannulation is effective for immune profiling in multiple sclerosis?

Research suggests that thoracic duct cannulation might help manage the immune system in people with multiple sclerosis (MS) by correcting immune imbalances. This trial will compare two approaches: 'In-and-out' catheterization and 'Indwelling' catheterization. The procedure involves collecting lymph fluid to understand immune cell activity in the body. Studies have shown that the composition of lymph fluid varies significantly in different illnesses, providing clues about the immune response. Although direct evidence for its effectiveness in treating MS is still being gathered, the procedure is minimally invasive and has proven useful for diagnosing other conditions. This suggests it might aid in better understanding and possibly managing MS symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

Amit Bar-Or, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults aged 18-40, both healthy and those with Multiple Sclerosis (MS) who are neurologically stable. MS patients must have been diagnosed per the McDonald criteria, have an EDSS score of 0-4, and be untreated or only on specific MS medications. Participants must understand English and not have used steroids recently.

Inclusion Criteria

My MS symptoms have not worsened in the last month.

I haven't taken any steroid medications in the last 4 weeks.

Written informed consent must be obtained before any assessment is performed.

Exclusion Criteria

I have a chronic immune system disease other than MS, or an immunodeficiency syndrome.

I have been diagnosed with neuromyelitis optica.

Your body has too few infection-fighting white blood cells.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants with MS receive Ofatumumab treatment and undergo lymphatic fluid collection via catheterization

3 weeks

Multiple time-point sampling

Follow-up

Participants are monitored for safety and immune cell profile changes after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Thoracic Duct Cannulation

Trial Overview The study involves collecting lymph fluid through thoracic duct cannulation to compare immune cells in MS patients versus healthy controls. It also examines changes in response to the FDA-approved therapy ofatumumab in MS patients.

How Is the Trial Designed?

Group I: 'In-and-out' catheterization Experimental Treatment 1 Intervention

Safety and immune-cell profile of lymphatic fluid in MS patients with a single time-point sampling of lymphatic fluids and peripheral blood compared to healthy controls. Two healthy controls and six patients with early MS (never treated or at least 90 days after discontinued treatment with glatiramer acetate or interferons), who consent to the 'In-and-out' catheter procedure. MS participants can also consent to OMB treatment with 2-year follow-up.

Group II: "Indwelling" catheterization Experimental Treatment 1 Intervention

immune-biology in people with MS before and during/after OMB treatment within thoracic duct and peripheral blood via indwelling catheter and multiple time-point sampling compared to healthy controls (without drug treatment). Twelve patients with early MS (never treated or at least 90 days after discontinued treatment with glatiramer acetate or interferons), who consent to treatment with OMB and to the indwelling catheter procedure with serial sampling and up to four healthy controls (no drug treatment)

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Novartis Institutes for BioMedical Research

Collaborator

Trials

5

Recruited

680+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05162638

Immune Profiles in Multiple Sclerosis (MS) Patients and ... In this study, lymph fluid will be collected by cannulation of the thoracic duct, a minimally invasive procedure performed by interventional radiologists.

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/38/NCT05162638/Prot_SAP_000.pdf

Research Protocol lymphoid fluid via thoracic duct cannulation in healthy people and people with. MS. ... Fluid sampling results will be assessed in both lymph ...

3. withpower.com withpower.com/trial/phase-multiple-sclerosis-2022-31307

Immune Profiling via Thoracic Duct Cannulation for ... The research suggests that drainage of the thoracic duct may help control the immune system in patients with multiple sclerosis by addressing immune imbalances ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022480416300506

Indications, techniques, and clinical outcomes of thoracic ... There is evidence that the composition of TD lymph undergoes significant changes in the presence of acute and critical illness.3, 4, 5, 11, 12, 13 The study of ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12110392/

Diagnostic Value of Multimodal Lymphatic Imaging ... Intraoperative findings from thoracic duct explorations confirmed the high diagnostic efficacy of these multimodal imaging techniques.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11265529/

Preliminary report of a thoracic duct-to-pulmonary vein ... Our primary aim was to develop a reproducible technique for creating a thoracic duct-to-pulmonary vein LVA that would remain patent and preserve ...