Clinical trial NCT06992401: Observational Study of Intranasal IVIG and RXRA Gene Expression in Long COVID Patients Undergoing Medical Tourism
Official title: An Observational Study Collecting Real-World Data on RXRA Gene Expression and Intranasal IVIG Treatment in Long COVID Patients With Immunodeficiency Engaged in International Medical Tourism
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Post-Acute Sequelae of SARS-CoV-2 Infection
Long COVID
Long COVID Fatigue
Long COVID Syndrome
COVID 19 Associated Coagulopathy
COVID-19 Vaccination
Keywords: RXRA gene
Intranasal IVIG
Real-world data
Medical tourism
Long COVID fatigue
Cytokine panel
Immunoglobulin therapy
Brain fog
Chronic inflammation
Real-world evidence
Global health
Post-viral syndrome
Immune recovery
Lead sponsor: Healing Hope International
Sponsor class: OTHER
First posted: 2025-05-28
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study enrolls adults aged 18 to 65 with persistent Long COVID symptoms and confirmed immunodeficiency, including low IgG/IgA or poor vaccine response. Participants must have elevated inflammatory markers and be free of active infections or neurological conditions. The population is observed while undergoing intranasal IVIG therapy internationally, with a focus on immunological, genetic, and quality of life outcomes.

Brief summary: This observational study is being conducted by Healing Hope International to collect real-world data on an emerging treatment approach for Long COVID in patients with immunodeficiency. The study explores the relationship between the RXRA gene and neuroinflammation and investigates the effects of intranasal immunoglobulin (IVIG) therapy in a real-world setting.

Participants will be individuals diagnosed with Long COVID who have confirmed immunodeficiency, such as low IgG or IgA levels or specific antibody deficiency. These individuals are receiving care through international clinical programs and will not receive any treatment as part of this study. Instead, Healing Hope will collect health information, clinical outcomes, and laboratory results from participating sites to better understand how intranasal IVIG might help reduce symptoms such as fatigue, brain fog, inflammation, and immune dysregulation.

The RXRA gene plays a role in regulating inflammation and immune response. Participants will also undergo genetic testing to assess RXRA expression and explore how it may be linked to recovery or ongoing symptoms.

The goal of this study is to contribute new insights into potential treatment options for Long COVID and to support responsible, science-backed care models for patients participating in medical tourism. No experimental drugs are being administered as part of this protocol. All treatment decisions are made independently by each clinical site. Data will be anonymized and used to advance knowledge in the field of immunological recovery and neuroinflammation.

Detailed description: This observational study, initiated by Healing Hope International, is designed to collect real-world data (RWD) from individuals diagnosed with Long COVID who are undergoing clinical care involving intranasal immunoglobulin (IVIG) therapy at international medical tourism sites. The objective is to better understand the relationship between RXRA gene expression and neuroinflammatory processes in immunodeficient individuals, and to evaluate the real-world impact of intranasal IVIG as a supportive therapy.

The RXRA gene encodes a nuclear receptor that regulates gene transcription involved in inflammation, lipid metabolism, and immune response modulation. Dysregulation of RXRA expression has been linked to inflammatory and neurodegenerative disorders. By correlating RXRA expression levels with immunological and symptomatic outcomes in a Long COVID population, this study seeks to clarify its relevance in chronic post-viral inflammation.

Eligible participants are adults (ages 18-65) with:

Persistent Long COVID symptoms for ≥12 weeks following SARS-CoV-2 infection,

Laboratory-confirmed immunodeficiency (e.g., low IgG/IgA, poor vaccine response, or specific antibody deficiency),

Elevated inflammatory biomarkers (e.g., CRP, cytokines),

No evidence of active infection (bacterial, viral, or fungal),

No comorbid neurological conditions (e.g., multiple sclerosis, Alzheimer's disease),

No current immunosuppressive therapies.

No investigational product will be administered by the study team. All treatments are prescribed and delivered independently by licensed international clinical sites. Healing Hope International operates as the sponsor and data coordinating center. Participants' data will be collected retrospectively and prospectively from site medical records, patient-reported surveys, and third-party laboratory assessments, including genetic testing for RXRA expression (e.g., via qPCR or NGS panels).

The primary data endpoints include:

RXRA gene expression levels,

Changes in immunological biomarkers (IgG/IgA, CRP, cytokine panel),

Clinical course of Long COVID symptoms (fatigue, cognitive impairment, respiratory issues),

Quality of life measures (collected via validated patient-reported outcome instruments).

The study complies with all applicable regulations for data protection and ethical research conduct, including informed consent, HIPAA-compliant data transfer where applicable, and de-identification of personal health information. Ethical approval will be obtained from an Institutional Review Board (IRB), and partner sites may obtain parallel local or national ethics approvals.

This study also seeks to characterize the broader landscape of medical tourism for regenerative therapies by mapping treatment accessibility, safety, and patient-reported effectiveness in the context of international care. It does not replace or compete with regulated clinical trials but aims to generate actionable real-world insights that can guide future controlled research.

The results of this study may help clarify the potential role of RXRA as a biomarker for neuroinflammation and assess the feasibility of intranasal IVIG as an adjunctive therapy for immune dysfunction in post-viral syndromes. By contributing to the body of evidence around global regenerative practices, this study supports the development of international ethical guidelines, compassionate use frameworks, and collaborative trial infrastructure in complex chronic conditions.

Eligibility criteria: Inclusion Criteria:

Age 18 to 65 years

Clinical diagnosis of Long COVID (symptoms persisting ≥12 weeks after SARS-CoV-2 infection)

Laboratory-confirmed immunodeficiency, including one or more of the following:

Low serum IgG and/or IgA

Specific antibody deficiency

Low pneumonia titers

Elevated inflammatory markers (e.g., CRP, cytokines)

No active infections at the time of enrollment (bacterial, viral, or fungal)

Negative for Lyme disease and NMDAR antibodies

Willingness to provide informed consent for data collection and use

Exclusion Criteria:

1. Current or recent active infection (e.g., viral, bacterial, or fungal)
2. Use of immunosuppressive therapy within the last 3 months
3. Active Infections: Participants with active infections, including viral, bacterial, or fungal infections, will be excluded.
4. Neurological Disorders: Participants with diagnosed neurological disorders, such as multiple sclerosis, Parkinson's disease, or Alzheimer's disease, will be excluded.
5. Immunosuppressive Therapy: Participants receiving immunosuppressive therapy will be excluded.
6. Inability to comply with study assessments or procedures

Primary outcomes:
measure: Change in Long COVID Symptom Severity Using Patient-Reported Outcome Measures (PROMs)
timeFrame: Baseline and 12 Weeks
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: StemSolutions
name: Dr. Anna L Kattan, MD: Regenerative Medicine
role: PRINCIPAL_INVESTIGATOR
References:
citation: VanElzakker MB, Bues HF, Brusaferri L, Kim M, Saadi D, Ratai EM, Dougherty DD, Loggia ML. Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by [11C]PBR28 PET correlates with vascular disease measures. Brain Behav Immun. 2024 Jul;119:713-723. doi: 10.1016/j.bbi.2024.04.015. Epub 2024 Apr 18.
citation: Alaiya A, Alshukairi A, Shinwari Z, Al-Fares M, Alotaibi J, AlOmaim W, Alsharif I, Bakheet R, Alharbi L, Allam R, Asiri A, Memish Z, Alromaih K, Al-Mozaini M. Alterations in the Plasma Proteome Induced by SARS-CoV-2 and MERS-CoV Reveal Biomarkers for Disease Outcomes for COVID-19 Patients. J Inflamm Res. 2021 Sep 1;14:4313-4328. doi: 10.2147/JIR.S322430. eCollection 2021.