Preoperative Steroids in Autoimmune Thyroid Disease

Randomized Controlled Trial of Preoperative Steroids in Autoimmune Thyroid Disease

This pilot project will randomize a small sample of patients about to undergo surgery for their autoimmune, inflammatory thyroid disease, and determine if a short course of prednisone alters the inflammation of the gland and makes surgery less difficult. It will enroll 30 participants who will each be on study for up to 7 months.

Study Overview

• Status: Completed
• Conditions: Thyroid Diseases
• Intervention / Treatment: Drug: Prednisone

Detailed Description

Graves' disease and Hashimoto's thyroiditis are autoimmune conditions affecting the thyroid gland. Surgery to remove the thyroid gland in these patients may be complicated by the inflammatory nature of these diseases. Prednisone is a steroid medication used to decrease inflammation of the thyroid gland in other disease states such as sub-acute thyroiditis, but has not been used systematically to reduce inflammation in patients about to undergo surgery.

This is a pilot project that proposes to randomize a small sample of patients about to undergo surgery for their autoimmune, inflammatory thyroid disease, and determine if a short course of prednisone alters the inflammation of the gland and makes surgery less difficult. This could potentially lead to better outcomes for these patients, as well as increased time to recovery and improved quality of life.

This project proposes to administer short quality of life surveys at three time points, as well as draw additional labs to measure inflammation and antibody levels at times when patients will already be getting labs drawn for clinical purposes. The purpose of this study is to generate preliminary data from which a larger, blinded, placebo-controlled trial could be designed.

These specific aims are:

• Determine the benefits and safety of preoperatively administered prednisone for patients with autoimmune thyroid disease undergoing thyroidectomy on:

  • Difficulty of surgery and rates of surgical complications
  • Serum autoantibody levels
• Longitudinally assess the impact of surgical treatment on QoL in patients with autoimmune thyroid disease

Update: Protocol amendment approved on 10-22-2020: Study team decided to omit the aim 'antibody-mediated cytokine levels' from the protocol and consent process as it became cost-prohibitive for processing and storage fees. Cytokine levels are not something typically collected or tracked in the course of clinical care, and may not be relevant. Study can proceed without this aim and will not alter the main outcome measures of antibody levels and difficulty of the operation.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Graves' disease or Hashimoto's disease with positive thyroid autoantibodies (Thyroglobulin Antibody [TgAb], Thyroid peroxidase antibody [TPO], Thyroid Stimulating Ig antibody [TSI], and/or Thyrotropin Receptor antibody [TRAb]).
• Participants will be invited to join the study after the decision has been made to proceed with thyroidectomy as the clinical treatment of their autoimmune thyroid disease.

Exclusion Criteria:

• Pediatric patients < 18
• Prior treatment with radioactive iodine (RAI)
• Known diagnosis of thyroid cancer
• Diabetic patients.
• Patients on any immunosuppressive regiment (such as organ transplant patients or patients treated for other autoimmune condition)
• Pregnant patients.
• Patients being treated for active infection.
• Any patient for whom the surgeon feels steroids would provide a clear benefit (ie. Extremely high auto-antibody levels with a very large, inflamed thyroid gland) will be treated according to the clinical judgement of the surgeon. If a surgeon feels steroids are indicated and prescribes them, the patient will not be eligible for the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Steroids; Participants randomized to the steroid arm will be given a prescription for prednisone 20mg daily for 7 days prior to surgery, otherwise, pre-operative standard of care	Drug: Prednisone; used to reduce inflammation; Other Names: steroid drug
No Intervention: No Steroids; Pre-operative Standard of Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thyroid Difficulty Scale Score	The surgeon will fill out the "Thyroid Difficulty Scale" at the conclusion of the operation. This is a 4-item survey to rate the vascularity, friability, mobility, and glandular size of the thyroid. The total possible range of scores from 4-20, higher scores indicate increased difficulty in thyroid surgery	surgery occurs up to 4 weeks, data collected a conclusion of operation
Percent Change From Baseline Mean in Autoantibody Levels	Autoantibodies that may be positive include: Thyroglobulin Antibody [TgAb], Thyroid peroxidase antibody [TPO], Thyroid Stimulating Ig antibody [TSI], and/or Thyrotropin Receptor antibody [TRAb]. Any that were positive pre-op will be measured at each time point. Baseline level will be 1.	baseline measure day of surgery (up to 4 weeks), up to 6 weeks (2 weeks post-op), up to 10 weeks (6 weeks post-op), up to 30 weeks (6 months post-op)
Change in Antibody-mediated Cytokine Levels	Antibody-mediated cytokine levels will be measured using a 10 cytokine panel from Luminex. Cytokines that have been implicated in other autoimmune disease include: IFN-gamma (BR29), IL-6 (BR13), IL-10 (BR22), IL-13 (BR47), IL-15 (BR63), IL-17A (BR42), and VEGF-C (BR38).	baseline (2-4 weeks prior to surgery), up to 4 weeks (Post Operative Day 1), up to 6 weeks (2 weeks post-op), up to 30 weeks (6 months post-op)
Change in Short Form Health Survey (SF-12) Mental Component Score (MCS)	The SF-12 is a 12-item quality of life survey to understand how the participant feels and how well they are able to do their normal activities, it is composed of the mental component score and the physical component score. Each is scored on a scale of 0-100, with higher numbers indicating higher quality of life.	baseline (2-4 weeks prior to surgery), up to 10 weeks (6 weeks post-op), up to 30 weeks (6 months post-op)
Change in Short Form Health Survey (SF-12) Physical Component Score (PCS)	The SF-12 is a 12-item quality of life survey to understand how the participant feels and how well they are able to do their normal activities, it is composed of the mental component score and the physical component score. Each is scored on a scale of 0-100, with higher numbers indicating higher quality of life.	baseline (2-4 weeks prior to surgery), up to 10 weeks (6 weeks post-op), up to 30 weeks (6 months post-op)
Change in Thyroid-specific Quality of Life Patient-reported Outcome Measure for Benign Thyroid Disorders (ThyPRO) Score	The ThyPRO survey is a quality of life measure designed to evaluate how thyroid disease has affected the participant's life. It is a 39-item survey that was scored from 0-4, higher scores indicate worse quality of life.	baseline (2-4 weeks prior to surgery), up to 10 weeks (6 weeks post-op), up to 30 weeks (6 months post-op)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ultrasound Doppler Quantification of Blood Flow		baseline (2-4 weeks prior to surgery), up to 4 weeks (Post Operative Day 1)
Surgical Complications: Parathyroid Hormone (PTH) Level	PTH is measured right after surgery to determine whether the nearby parathyroid glands were injured during surgery. Low PTH levels immediately after surgery are concerning for symptomatic low calcium levels, either temporarily or permanent, after thyroidectomy. Normal PTH is typically between 20-70.	immediately after surgery (baseline for all participants)
Number of Participants With Surgical Complications: Recurrent Laryngeal Nerve (RLN) Injury		up to 4 weeks (Post Operative Day 1)

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Dawn K Elfenbein, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Actual): October 4, 2022
• Study Completion (Actual): October 4, 2022

Study Registration Dates

• First Submitted: September 1, 2020
• First Submitted That Met QC Criteria: September 8, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Autoimmune disease; Graves' Disease; Hashimoto's Thyroiditis
• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: 2020-0209; Protocol Ver October 2020 (Other Identifier: UW Madison); A539711 (Other Identifier: UW Madison); SMPH/SURGERY/ENDOCRINE (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: Yes
• Studies a U.S. FDA-regulated device product: No