Vitamin A Status in Patients With Vocal Fold Leukoplakia

This study will determine systemic vitamin A status and lesion histopathology of participants with vocal fold hyperkeratosis resulting in clinical leukoplakia.

Study Overview

• Status: Enrolling by invitation
• Conditions: Vitamin A Deficiency; Leukoplakia; Vitamin A; Vocal Cord Neoplasm

Detailed Description

The investigator's overarching goal is to determine if there is a pathophysiologic rationale for vitamin A supplementation in the treatment of vocal fold hyperkeratosis. Vocal fold hyperkeratosis is an accumulation of epithelial surface keratin resulting in clinical leukoplakia. It is primarily managed using destructive techniques that risk iatrogenic injury, fibrosis, and voice impairment. Given the potential morbidity of biopsy and lesion removal, there is a need for new approaches to the prevention and treatment of vocal fold leukoplakic disorders that are non-destructive. Vitamin A is a key regulator of epithelial health and systemic vitamin A deficiency could directly contribute to hyperkeratosis. Based on vitamin A's importance to vocal fold stellate and epithelial cell biology and its direct relevance to vocal fold hyperkeratosis, this study will assess vitamin A status in participants with vocal fold hyperkeratosis. An association would suggest further study on the effects of vitamin A optimization and/or supplementation in patients with leukoplakia, as well as an adjuvant therapy in participants for whom surgical treatment is indicated.

• Study Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospitals and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Potential participants will be identified from the active caseloads of speech-language pathologists or otolaryngologists. During a routine clinical encounter, a member of the clinical team will inform potential participants of the research opportunity.

Description

Inclusion Criteria:

1. Willing to provide informed consent.
2. Willing to comply with all study procedures and be available for the duration of the study.
3. Ability to take oral medication.
4. At least 18 years of age.

5. Leukoplakia study groups:

   1. Leukoplakia due to hyperkeratosis with dysplasia: biopsy-confirmed diagnosis of hyperkeratosis with dysplasia.
   2. Leukoplakia due to hyperkeratosis with no dysplasia: biopsy-confirmed diagnosis of hyperkeratosis with no dysplasia.
6. Control group: Laryngoscopy showing no evidence of vocal fold mucosal disease.

Exclusion Criteria:

1. History of malignant vocal fold mucosal pathology.
2. History of metabolic or liver disorder.
3. History of anorexia or bulimia.
4. Pregnant, lactating, or planning on becoming pregnant during the study period.
5. History of >4.5 kg weight loss in the past 90 days.
6. Medical or other inability to complete an 8 hour fast.
7. Acute respiratory or gastrointestinal illness.
8. Currently incarcerated.
9. Impaired decision-making capacity.
10. No or limited English speaking ability; illiterate or low-literacy ability.
11. Profound visual or hearing impairment that limits written or verbal communication.
12. Status relationship with a member of the study team.
13. Not suitable for study participation due to other reasons at the discretion of the investigators.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Leukoplakia due to hyperkeratosis with dysplasia; Biopsy-confirmed diagnosis of hyperkeratosis with dysplasia.
Leukoplakia due to hyperkeratosis with no dysplasia; Biopsy-confirmed diagnosis of hyperkeratosis with no dysplasia.
Control group; Laryngoscopy showing no evidence of vocal fold mucosal disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vitamin A liver reserves	Total vitamin A liver concentration determined using retinol stable isotope dilution (μmol/g)	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum retinol	Serum retinol concentration (μmol/L)	Baseline
Serum retinyl esters	Serum retinyl esters concentration (μmol/L)	Baseline
Serum carotenoids	Serum carotenoid concentrations (μmol/L)	Baseline

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Institute on Deafness and Other Communication Disorders (NIDCD)
• Investigators: Principal Investigator: Nathan Welham, PhD, CCC-SLP, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 15, 2022
• First Submitted That Met QC Criteria: April 11, 2022
• First Posted (Actual): April 12, 2022

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Eye Diseases; Nutrition Disorders; Pathological Conditions, Anatomical; Avitaminosis; Deficiency Diseases; Malnutrition; Precancerous Conditions; Vision Disorders; Night Blindness; Vitamin A Deficiency; Leukoplakia
• Other Study ID Numbers: 2021-1045 (Other Identifier: UW Madison); A539770 (Other Identifier: UW, Madison); SMPH/SURGERY/SURGERY*OT (Other Identifier: UW Madison); R01DC019357 (U.S. NIH Grant/Contract); 07/01/2021 (Other Identifier: UW Madison)

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