Levothyroxine Sodium in Thyroidectomized Patients Taking Proton Pump Inhibitors

An Open-label Therapeutic Efficacy Study of Tirosint (Levothyroxine Sodium) Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors

This is an open-label therapeutic efficacy study of Tirosint (levothyroxine sodium) capsules in thyroidectomized patients taking proton pump inhibitors and levothyroxine, evaluating changes in serum levels of Thyroid Stimulating Hormone (TSH) upon switch to Tirosint with respect to baseline.

Study Overview

• Status: Completed
• Conditions: Hypothyroidism;Postablative
• Intervention / Treatment: Drug: levothyroxine sodium capsule; Drug: Proton pump inhibitor (PPI); Drug: Levothyroxine Sodium (LT4) Tablets

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • California Head and Neck Specialists
    • Ventura, California, United States, 93003
      • Coastal Metabolic Research Centre
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2975
      • Washington Hospital Center
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • MedStar Union Memorial Hospital
  • New York
    • New York, New York, United States, 11432
      • NYC Health + Hospitals/ Queens
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Diabetes & Endocrinology Consultants, PC
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • Carolina Ear Nose and Throat Clinic
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Washington
    • Federal Way, Washington, United States, 98003
      • Stonesifer Endocrine Care & Clinical Research Inc., PS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. written informed consent duly read, signed and dated by the subject;
2. aged ≥18 and ≤65 years;
3. history of hypothyroidism due to total thyroidectomy;
4. on stable LT4 doses for at least 6 weeks at screening (≥88 mcg daily and ≤250 mcg daily);
5. TSH at screening ≥0.3 and ≤4.0 mIU/L;
6. history of gastroesophageal reflux disease or associated gastrointestinal issues on prescription PPIs (i.e. omeprazole ≥20 mg daily, or esomeprazole ≥ 20 mg daily, or lansoprazole ≥ 15 mg daily, or pantoprazole ≥ 40 mg daily) for at least 8 weeks before screening visit and for whom chronic therapy with PPIs for the next 5 months has been prescribed;
7. for women, adequate and continuative contraceptive measures until the end of the study, if not in menopause;
8. reasonable assumption of understanding the study and willingness to take part to the study and to comply with protocol requirements.

Exclusion Criteria:

1. suspected or ascertained non-compliance with LT4 or PPI therapy;
2. subject requiring changes of levothyroxine dose;
3. use of over-the-counter (OTC) PPIs;
4. history of malabsorption or history of gastric bypass surgery, short-gut syndrome, inflammatory bowel disease and other conditions of the gastrointestinal tract that may affect drug absorption (e.g. celiac disease)3;
5. multiple co-morbidities (e.g. cardiac heart failure, active arrhythmia or history of arrhythmia, particularly atrial fibrillation, uncompensated diabetes mellitus, uncorrected adrenal insufficiency, seriously compromised hepatic, renal and/or respiratory functions);
6. neoplastic pathology, active or in remission for less than 5 years (excluding the basic thyroid pathology);
7. terminal condition;
8. parenteral or assisted enteral feeding;
9. presence of any medical condition or other circumstances which would significantly affect the safety of the subject or decrease the chance of obtaining reliable data, achieving study objectives or completing the study;
10. history of alcoholism, drug abuse or psychiatric diseases that could invalidate the informed consent or limit the subject compliance with protocol requirements;
11. pregnant (positive urine pregnancy test at screening or baseline visits) or breast-feeding subject or subject planning a pregnancy in the next months;
12. known hypersensitivity to the ingredients of the preparation involved in the study3;
13. use of forbidden concomitant medications;
14. regular consumption of soy and soy derivatives, cotton seed meals, walnuts, and dietary fibres;
15. participation in other clinical studies during the 3 months prior to screening;
16. presumption of poor reliability/cooperation;
17. any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: levothyroxine sodium capsules; levothyroxine sodium capsules 88 to 250 mcg/day (depending on individual needs) for 3 months

Drug: levothyroxine sodium capsule; after the run-in period, patients will be switched to levothyroxine sodium capsule at the same dose used during run-in; Other Names: Tirosint; Drug: Proton pump inhibitor (PPI); for the whole study duration all subjects will keep taking their proton pump inhibitor medication, as per prescription and as before inclusion; Other Names: omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, rabeprazole; Drug: Levothyroxine Sodium (LT4) Tablets; during the run-in period, subjects will continue taking their levothyroxine sodium tablet medication as per prescription and as before inclusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thyroid Stimulating Hormone (TSH)	Change in Serum Levels of TSH (Thyroid Stimulating Hormone) from Baseline	baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Free Thyroxine (FT4)	Change in Serum Levels of FT4 (free thyroxine) from Baseline	baseline and 12 weeks
Total Thyroxine (TT4)	Change in Serum Levels of TT4 (total thyroxine) from Baseline	baseline and 12 weeks
Free Triiodothyronine (FT3)	Change in Serum Levels of FT3 (free triiodothyronine) from Baseline	baseline and 12 weeks
Total Triiodothyronine (TT3)	Change in Serum Levels of TT3 (total triiodothyronine) from Baseline	baseline and 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Creatine Phosphokinase (CPK)	Change in Serum Levels of creatine phosphokinase (CPK) from Baseline	baseline and 12 weeks
Sex Hormone Binding Globulin (SHBG)	Change in Serum Levels of SHBG (sex hormone binding globuline) from Baseline	baseline and 12 weeks
Ferritin	Change in Serum Levels of ferritin from Baseline	baseline and 12 weeks
Angiotensin Converting Enzyme (ACE)	Change in Serum Levels of ACE (angiotensin converting enzyme) from Baseline	baseline and 12 weeks
Triglycerides	Change in triglycerides levels from Baseline	baseline and 12 weeks
Cholesterol, Total	Change in total cholesterol levels from Baseline	baseline and 12 weeks
Low Density Lipoprotein (LDL)-Cholesterol	Change in low density lipoprotein (LDL)-cholesterol levels from baseline	baseline and 12 weeks
High Density Lipoprotein (HDL)-Cholesterol	Change in High Density Lipoprotein (HDL)-cholesterol levels from baseline	baseline and 12 weeks
Very Low Density Lipoprotein (VLDL)-Cholesterol	Change in Very Low Density Lipoprotein (VLDL)-cholesterol levels from baseline	baseline and 12 weeks

Collaborators and Investigators

• Sponsor: IBSA Institut Biochimique SA
• Investigators: Principal Investigator: Kenneth D Burman, MD, MedStar Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2018
• Primary Completion (Actual): June 15, 2020
• Study Completion (Actual): June 15, 2020

Study Registration Dates

• First Submitted: March 17, 2017
• First Submitted That Met QC Criteria: March 22, 2017
• First Posted (Actual): March 29, 2017

Study Record Updates

• Last Update Posted (Actual): April 5, 2022
• Last Update Submitted That Met QC Criteria: April 1, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Hypothyroidism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Dexlansoprazole; Lansoprazole; Rabeprazole; Omeprazole; Esomeprazole; Pantoprazole; Proton Pump Inhibitors
• Other Study ID Numbers: 13US-T404

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
• product manufactured in and exported from the U.S.: No