Theophylline Nasal Spray for Loss of Smell

Overseen By Brigette S Vaughan, MSN, APRN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Nebraska

Must not be taking: Intranasal medications, Theophylline

Disqualifiers: Substance use disorder, Active malignancy, Chronic sinusitis, others

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

Compensation: Varies

Number of Visits: 5

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a nasal spray with theophylline can help people regain their sense of smell, specifically if lost due to Parkinson's Disease. Participants will use the spray for about six months, with regular check-ins to monitor progress and any side effects. The trial seeks individuals who have experienced a reduced or lost sense of smell for over six months due to Parkinson's and have no nasal issues like polyps or infections. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Do I need to stop taking my current medications for the trial?

You may need to stop taking certain medications, especially those administered intranasally, except for nasal saline. If you're using theophylline or any investigational drugs, you must stop them before joining the trial. Always discuss with the study team to ensure your current medications are allowed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that using theophylline as a nasal spray is generally safe. Studies have found it safer and more effective for improving smell and taste than oral theophylline. As a nasal spray, it has been well-tolerated with few side effects. In trials, participants experienced improved smell function without major negative effects. Although this study is still in the early stages, other research suggests that this treatment is likely safe for participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for loss of smell, which often involve steroids or smell training, the theophylline nasal spray introduces a unique approach by utilizing the active ingredient theophylline directly in the nasal passages. This method targets the olfactory receptors more precisely, potentially offering a more direct and effective restoration of smell. Researchers are excited because this targeted delivery system could lead to quicker and more noticeable improvements, making it a promising alternative to current therapies.

What evidence suggests that theophylline nasal spray might be an effective treatment for loss of smell in Parkinson's Disease?

Research has shown that theophylline nasal spray, which participants in this trial will receive, might help improve the sense of smell. In one study, half of the people using theophylline showed significant improvement in their smell test results. Another study found that theophylline nasal spray worked better for enhancing taste and smell than taking it as a pill. However, results can vary. Some individuals who lost their sense of smell due to COVID-19 experienced mixed outcomes with the spray. Overall, early research suggests it could be promising for improving smell in certain situations. ^{2 5 6 7 8}

Who Is on the Research Team?

Mara Seier, MD

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

This trial is for adults aged 19-80 with Parkinson's Disease who have lost their sense of smell or have a reduced ability to smell. Participants will use the study nasal spray twice daily and attend regular check-ups.

Inclusion Criteria

Able to provide written informed consent

Hyposmia defined as ≤5 on the NRS-11 smell scale (scale of 0-10; 10 indicating normal sense of smell, 0 indicating no sense of smell)

A MOCA score >24

Exclusion Criteria

I have visible signs or symptoms of a chronic sinus or respiratory infection.

I need nasal sprays or drops for my severe allergy symptoms.

My main issue is distorted smell perception.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intranasal theophylline (CYR-064) nasal spray for 24 weeks to improve sense of smell

24 weeks

4 visits (in-person) every 2 weeks during the first month, followed by monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 follow-up phone call

What Are the Treatments Tested in This Trial?

Interventions

• Theophylline Nasal Spray

Trial Overview The trial tests if CYR-064, a theophylline-based nasal spray, can improve the sense of smell in those affected by hyposmia or anosmia due to Parkinson's Disease. It involves using the spray over a period of 24 weeks with follow-up visits.

How Is the Trial Designed?

Group I: Intranasal Theophylline Experimental Treatment 1 Intervention

Theophylline Intranasal Spray strength 3.1mg/mL, providing a per spray dose of 140 microgram and total daily dose of 1120 microgram per day (2 sprays per naris BID). Intervention is self-administered.

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35797024/

The SCENT2 Phase 2 Randomized Clinical Trial - PubMed Eleven (50%) participants in the theophylline arm and 6 (26%) in the placebo arm had a change of 4 or more points in UPSIT scores from baseline ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04789499

Smell in Covid-19 and Efficacy of Nasal Theophylline Currently, up to 80% of patients report subjective olfactory dysfunction (OD), and prevalence using objective olfactory testing could be even higher. We propose ...

3. jamanetwork.com jamanetwork.com/journals/jamaotolaryngology/fullarticle/1392510

Intranasal Theophylline Treatment of Hyposmia and ... Intranasal theophylline treatment improved taste and smell acuity in 8 patients after 4 weeks, with improvement greater than after oral administration. No ...

4. cidrap.umn.edu cidrap.umn.edu/mixed-results-nasal-theophylline-treat-covid-related-loss-smell

Mixed results for nasal theophylline to treat COVID-related ... After 4 weeks of theophylline treatment, 4 of 10 participants reported somewhat improved smell, and 6 said their olfaction remained the same.

5. jacionline.org jacionline.org/article/S0091-6749(16)32328-4/fulltext

Intra-Nasal Theophylline for the Treatment of Chronic ... To evaluate the efficacy of intra-nasal theophylline therapy (ITp) in improving smell in subjects with chronic hyposmia/anosmia.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9264240/

Efficacy and Safety of Saline Nasal Irrigation Plus ... The use of theophylline added to saline nasal irrigations may result in clinically beneficial improvements in smell function compared with ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06498687?cond=hyposmia&rank=4

Theophylline Nasal Spray for PD-Related Hyposmia and ... The goal of this study is to learn if intranasal theophylline (CYR-064) improves sense of smell in participants with hyposmia or anosmia related to the ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0196070921004002

Smell Changes and Efficacy of Nasal Theophylline ... To evaluate the efficacy and safety of intranasal theophylline saline irrigation on olfactory recovery in patients with post-viral olfactory dysfunction (PVOD).