Cognitive and Immunologic Profiles of Patients With Olfactory Dysfunction After Smell Training (CIPOD)

A research study to assess the baseline olfactory function, mental health status, clinical severity, and immunological profile in patients with smell loss. The impact of a 3-month olfactory training program on smell function, immunological changes, and mental health in patients with smell loss will be evaluated.

The primary purpose of this study is to investigate tissue and blood samples to identify molecules that may be related to smell loss, ultimately aiming to develop future treatments for this condition and correlate with cognition.

Study Overview

• Status: Recruiting
• Conditions: Smell Loss; Chronic Rhinosinusitis (CRS)
• Intervention / Treatment: Other: Smell Training

Detailed Description

Adult patients with chronic rhinosinusitis (CRS) with nasal polyps and those experiencing loss of smell will be recruited for the study, along with healthy control participants. We will exclude individuals with unilateral nasal polyps, autoimmune diseases, ciliary disorders, cystic fibrosis, or smell loss due to tumors or trauma.

Assessments will be conducted at baseline and again three months after smell training to evaluate changes in olfactory function. Control patients will only undergo baseline testing with no follow-up assessments needed.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: John O'Neill; Phone Number: 4405062611; Email: ONEILLJ2@ccf.org
• Study Contact Backup: Name: Christopher Novicky; Phone Number: 216-444-7018; Email: novickc@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • The Cleveland Clinic
      • Contact: John O'Neill; Phone Number: 4405062611; Email: ONEILLJ2@ccf.org
      • Contact: Hana Rosen; Phone Number: 216-444-7018; Email: rosenh@ccf.org
      • Principal Investigator: Mohamad Chaaban

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age less than 18 years-old
• Present to rhinology clinic with CRS with nasal polyps
• Sense of smell loss for any reason (other than trauma or tumor)

Exclusion Criteria:

• Patients < 18 years of age
• Individuals with unilateral nasal polyps
• Autoimmune diseases
• Ciliary disorders
• Cystic fibrosis
• Smell loss due to tumors or trauma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1: - loss of smell + CRS with nasal polyps (CRSwNP); Loss of smell + CRS with nasal polyps (CRSwNP)	Other: Smell Training; Patients experiencing loss of smell from chronic rhinosinusitis (CRS)will undergo smell training.
Active Comparator: Group 2: - loss of smell with no CRS/no polyps - undergo 3 months of smell training; Loss of smell + CRS with nasal polyps (CRSwNP) - undergo 3 months of smell training	Other: Smell Training; Patients experiencing loss of smell from chronic rhinosinusitis (CRS)will undergo smell training.
No Intervention: Control Group 1: - no loss of smell CRS with nasal polyps (CRSwNP); No loss of smell CRS with nasal polyps (CRSwNP)
No Intervention: Control Group 2: -no loss of smell / no CRS/no polyps; No loss of smell / no CRS/no polyps

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome Measure 1: Baseline olfactory function measured by UPSIT score	At baseline, participants will complete the University of Pennsylvania Smell Identification Test (UPSIT), a standardized 40-item scratch-and-sniff odor identification test. Scores range from 0 to 40, with higher scores indicating better olfactory function. Unit of Measure: Score on a scale from 0 to 40.	Baseline
Primary Outcome Measure 2: Baseline quality-of-life impact of olfactory dysfunction measured by QOD-NS score	At baseline, participants will complete the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS), which measures the negative psychosocial impact of olfactory dysfunction. Scores range from 0 to 48, with higher scores indicating greater negative impact of smell loss on quality of life. Unit of Measure: Score on a scale from 0 to 48.	Baseline
Primary Outcome Measure 3: Baseline cognitive function measured by MMSE score	At baseline, participants will complete the Mini-Mental State Examination (MMSE), an 11-question cognitive screening tool. Scores range from 0 to 30, with higher scores indicating better cognitive function. Unit of Measure: Score on a scale from 0 to 30.	Baseline
Primary Outcome Measure 4: Baseline nasal cytokine concentration	At baseline, nasal secretions will be collected from the middle meatus using a polyvinyl alcohol (PVA) sponge and analyzed for cytokine concentrations by multiplex immunoassay. Each cytokine concentration will be reported separately and will not be combined with questionnaire or cognitive assessment scores. Unit of Measure: pg/mL for each cytokine concentration reported separately.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcome Measure 1: Change from baseline to Month 3 in olfactory function measured by UPSIT score	Change from baseline to Month 3 in olfactory function will be assessed using the University of Pennsylvania Smell Identification Test (UPSIT), a standardized 40-item scratch-and-sniff odor identification test. Scores range from 0 to 40, with higher scores indicating better olfactory function. Unit of Measure: Change in score on a scale from 0 to 40.	Baseline to Month 3
Secondary Outcome Measure 2: Change from baseline to Month 3 in quality-of-life impact of olfactory dysfunction measured by QOD-NS score	Change from baseline to Month 3 in the negative psychosocial impact of olfactory dysfunction will be assessed using the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS). Scores range from 0 to 48, with higher scores indicating greater negative impact of smell loss on quality of life. Unit of Measure: Change in score on a scale from 0 to 48.	Baseline to Month 3
Secondary Outcome Measure 3: Change from baseline to Month 3 in cognitive function measured by MMSE score	Change from baseline to Month 3 in cognitive function will be assessed using the Mini-Mental State Examination (MMSE), an 11-question cognitive screening tool. Scores range from 0 to 30, with higher scores indicating better cognitive function. Unit of Measure: Change in score on a scale from 0 to 30.	Baseline to Month 3
Secondary Outcome Measure 4: Change from baseline to Month 3 in nasal cytokine concentration	Change from baseline to Month 3 in nasal cytokine concentration will be assessed. Nasal secretions will be collected from the middle meatus using a polyvinyl alcohol (PVA) sponge and analyzed by multiplex immunoassay. Each cytokine concentration will be reported separately. Unit of Measure: Change in pg/mL.	Baseline to Month 3

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Mohamad Chaaban, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: May 13, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Chronic Rhinosinusitis; CRSwNP; Smell Loss; Nasal Polyps
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Pathological Conditions, Anatomical; Respiratory Tract Diseases; Nose Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Polyps; Olfaction Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Anosmia; Nasal Polyps; Therapeutics; Olfactory Training
• Other Study ID Numbers: IRB #24-1122

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No