30 Participants Needed

Mucus Clearance Therapy for Primary Ciliary Dyskinesia

CN
SA
Overseen BySara Abu-Nasser, DO
Age: Any Age
Sex: Any
Trial Phase: Phase < 1
Sponsor: University of North Carolina, Chapel Hill
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

The purpose of this study is to measure mucociliary clearance (MCC) in groups of subjects with the disease Primary Ciliary Dyskinesia (PCD) caused by mutations in different genes, and compare to healthy subjects. Some of these genes are associated with a milder clinical phenotype. This study seeks to determine if the milder phenotype is a result of mutations in a set of specific genes. The hypothesis is that subjects with PCD caused by mutations in the milder group will maintain a low, but significant rate of mucociliary clearance, while patients with mutations in genes in the more severe group will have a complete absence of mucociliary clearance. These studies will help inform future treatment strategies.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications that may impact the study results, including steroids, beta antagonists, non-steroidal anti-inflammatory agents, beta-blocking medications, multivitamins, Vitamin C or E, and herbal medications. There is a specific period of 4 days before the treatment visit during which some of these medications should not be taken.

What data supports the effectiveness of the treatment for mucus clearance in Primary Ciliary Dyskinesia?

The study on adrenergic stimulation showed that similar drugs can enhance mucus clearance in the airways, suggesting that treatments like Albuterol and Salbutamol, which are adrenergic agonists, may help improve mucus clearance in conditions like Primary Ciliary Dyskinesia.12345

Is Mucus Clearance Therapy using Tc-99m sulfur colloid safe for humans?

There is a report of an allergic reaction in a patient after injecting Tc-99m sulfur colloid, suggesting that while generally used safely, there may be rare allergic reactions.15678

How does the mucus clearance treatment for primary ciliary dyskinesia differ from other treatments?

This treatment is unique because it involves the use of a nebulized epithelial sodium channel (ENaC) blocker, idrevloride, which helps improve lung function by blocking sodium channels to keep mucus hydrated and easier to clear, unlike other treatments that may not target this specific mechanism.134910

Research Team

LO

Lawrence Ostrowski, PhD

Principal Investigator

University of North Carolina at Chapel Hil

Eligibility Criteria

This trial is for adults over 18 with Primary Ciliary Dyskinesia (PCD) due to specific genetic mutations. Participants need a confirmed PCD diagnosis, normal lung function tests, and no other lung diseases like asthma or cystic fibrosis. Women must not be pregnant unless they've had certain surgeries.

Inclusion Criteria

I am 18 years old or older.
Subjects must have an FVC, FEV1 and FVC/FEV1 of at least 80% of predicted. Subjects who fall out of the normal range will be offered a copy of the test to share with their personal physician.
Forced Expiratory Volume (FEV1) of at least 30 percent of predicted
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Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day
1 visit (in-person)

Baseline Measurement

Participants undergo baseline mucociliary clearance measurement using radiolabeled Tc99m-sulfur colloid and gamma imaging

60 minutes
1 visit (in-person)

Post-Albuterol Measurement

Participants receive Albuterol and undergo further mucociliary clearance measurement

60 minutes
1 visit (in-person)

Cough Clearance Measurement

Participants perform cough clearance assessment over a 30-minute period using gamma imaging

30 minutes
1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the study procedures

1 day

Treatment Details

Interventions

  • Albuterol
  • Technetium99m - Sulfur Colloid (Tc99m-SC)
Trial OverviewThe study measures how well mucus clears from the lungs in PCD patients with different gene mutations compared to healthy people. It aims to see if some genes cause milder symptoms by allowing some mucociliary clearance versus none at all, which could guide future treatments.
Participant Groups
3Treatment groups
Active Control
Group I: Genotypes associated mild phenotypeActive Control2 Interventions
Subjects with 2 confirmed mutations in RSPH1, Radial Spoke Head Component 9 (RSPH9), Radial Spoke Head Component 4A (RSPH4a), or Dynein Axonemal Heavy Chain 11 (DNAH11). This group may also include subjects with mutations in newly identified genes that are associated with a milder clinical phenotype.
Group II: Genotypes associated with severe phenotypeActive Control2 Interventions
Subjects with 2 confirmed mutations in DNAH5, Dynein Axonemal Intermediate Chain 1 (DNAI1), Coiled-Coil Domain Containing 39 (CCDC39), or Coiled-Coil Domain Containing 40 (CCDC40). This group may also include subjects with mutations in newly identified genes that are associated with a more severe clinical phenotype.
Group III: Healthy ControlActive Control2 Interventions
Healthy subjects with no pre-existing lung disease.

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials
1,588
Recruited
4,364,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials
3,987
Recruited
47,860,000+

Findings from Research

In a study involving halothane-anesthetized dogs, bronchial retention of submicrometer technetium-99m-labeled sulfur colloid particles was found to be 8.5% at 3 hours and 1.5% at 24 hours post-deposition, indicating that most particle clearance occurs within the first 3 hours.
The study demonstrated that clearance mechanisms differ between particle types: sulfur colloid particles cleared primarily through mucociliary transport, while unbound technetium-99m pertechnetate cleared more rapidly via transepithelial absorption.
Retention of insoluble particles after local intrabronchial deposition in dogs.Lay, JC., Berry, CR., Kim, CS., et al.[2017]
Inhalation of terbutaline sulphate, an adrenergic agonist, did not significantly enhance the clearance of particles from the bronchioles in 10 healthy subjects, indicating that this treatment may not be effective for stimulating mucociliary transport in the smallest airways.
The study suggests that mucociliary transport is not a major mechanism for clearing mucus from bronchioles, implying that other mechanisms may play a more critical role in mucus clearance in these areas.
Effect of adrenergic stimulation on clearance from small ciliated airways in healthy subjects.Svartengren, K., Philipson, K., Svartengren, M., et al.[2019]
Mucociliary transport can be effectively evaluated using inhaled technetium-99m labeled sulfur colloid to measure clearance rates.
In a case study of a patient with recurrent sinusitis and infertility, abnormal mucociliary clearance suggested a potential diagnosis of Kartagener syndrome, highlighting the importance of this assessment in understanding respiratory conditions.
Abnormal mucociliary transport study in a patient with Kartagener syndrome.Taylor, RE.[2016]

References

Retention of insoluble particles after local intrabronchial deposition in dogs. [2017]
Effect of adrenergic stimulation on clearance from small ciliated airways in healthy subjects. [2019]
Abnormal mucociliary transport study in a patient with Kartagener syndrome. [2016]
Mucociliary clearance in patients with cystic fibrosis and in normal subjects. [2006]
Radiation dose calculations for inhalation of Tc-99m sulfur colloid radioaerosol. [2013]
Stability of a mixture of technetium Tc 99m sulfur colloid and lidocaine hydrochloride. [2019]
Adverse reaction to 99Tcm sulfur colloid in a routine examination. A case report. [2015]
Sulfur dioxide and tracheobronchial clearance in man. [2019]
Mucociliary transport using 99mTc-albumin colloid: a reliable screening test for primary ciliary dyskinesia. [2018]
Safety and efficacy of the epithelial sodium channel blocker idrevloride in people with primary ciliary dyskinesia (CLEAN-PCD): a multinational, phase 2, randomised, double-blind, placebo-controlled crossover trial. [2023]