Efficacy and Safety of Cholestyramine and Prednisolone as Adjunctive Therapy in Treatment of Overt Hyperthyroidism (ChoPS)

October 1, 2017 updated by: Clinical Research Centre, Malaysia

A Multi-center, Open Label, Randomised Parallel- Group Study to Compare the Efficacy of Cholestyramine Plus Standard Treatment Versus Prednisolone Plus Standard Treatment Versus Standard Treatment Alone in Treatment of Overt Hyperthyroidism

Hyperthyroidism is the second most common endocrine disorder in the world with Graves' disease being the commonest. Anti thyroid drugs including methimazole, carbimazole, and propylthiouracil are effective treatments but take in most cases between 6 to 8 weeks to achieve euthyroidism. This study aim to assess the efficacy of cholestyramine and prednisolone as adjunctive treatment to standard treatment in patients with overt hyperthyroidism in 4 weeks.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Hyperthyroidism is the second most common endocrine disorder in the world with an estimate prevalence rate of 0.5-1.3% with Graves' disease being the commonest cause.

Uncontrolled hyperthyroidism results in increase cardiovascular morbidity and mortality primarily due to heart failure and thromboembolism. Therefore treatment is essential to restore a euthyroid state in order to reverse the cardiovascular complications.

Anti thyroid drugs (ATDs) including methimazole, carbimazole, and propylthiouracil are effective treatments that inhibit thyroid hormone synthesis, and have clinically important immunosuppressive effects including reducing serum antithyrotropin receptor antibody (TRAb) concentration with time but take in most cases between 6 to 8 weeks to achieve euthyroidism. Therefore there may be a role for adjunctive treatment added on to ATDs. It may be situations where adjunctive treatment is required to alleviate symptoms and restore euthyroidism rapidly such as before surgery or radioactive iodine treatment or in vulnerable groups such as the elderly or those with serious thyrotoxic complications.

This study aim to assess the efficacy of cholestyramine and prednisolone as adjunctive treatment to standard treatment in patients with overt hyperthyroidism in 4 weeks. Cholestyramine is an anion exchange resin that binds thyroxine (T4) in the intestine resulting in fecal excretion of T4 thus reducing the enterohepatic circulation and absorption in hyperthyroidism. Steroids have been shown to be effective in controlling hyperthyroidism by inhibiting the conversion of thyroxine to triiodothyronine peripherally and also blocks the release of thyroxine from the thyroid gland. It may also have the potential to suppress the immune response and hence decrease stimulation of the thyroid gland in Graves.

135 patients with moderate to severe uncontrolled overt hyperthyroid patients secondary to Graves disease will be randomized into 3 groups. Group 1 patients will be treated with cholestyramine 4g twice a day plus carbimazole and propanolol for 4 weeks. Group 2 patients will be treated with prednisolone 30 mg daily for week 1, 20 mg daily for week 2, 10 mg daily for week 3 and 5 mg daily for week 4 plus carbimazole and propanolol for 4 weeks. Group 3 patients will be treated with carbimazole 30 mg daily and propanolol 40 mg bd for 4 weeks. Patients will have their clinical status (weight, blood pressure, pulse rate) measured at baseline along with a TRAb level and Free Triiodotyronine (T3), Free T4 and Thyroid stimulating hormone (TSH) levels. They will be evaluated at week 2 and week 4 of intervention period and have their clinical status (weight, blood pressure, pulse rate) and laboratory (Free T3, Free T4, TSH, Potassium, Fasting/random blood glucose) measured. Adverse events will be monitored at week 2, 4, and 6.

Study Type

Interventional

Enrollment (Anticipated)

135

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Malaysia
    • Sabah
      • Kota Kinabalu, Sabah, Malaysia, 88300
        • Recruiting
        • Hospital Queen Elizabeth 2
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Pei Lin Chan, Dr.
    • Selangor
      • Ampang, Selangor, Malaysia, 68000
        • Recruiting
        • Hospital Ampang
        • Contact:
    • Wilayah Persekutuan
      • Putrajaya, Wilayah Persekutuan, Malaysia, 62250
        • Recruiting
        • Hospital Putrajaya
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Siti A Alias, Dr
        • Sub-Investigator:
          • Lisa Mohamed Nor, Dr
        • Sub-Investigator:
          • Rashidah Bahari, Dr
        • Sub-Investigator:
          • Nurul Z Badarudin, Dr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Provision of written consent by subject or guardian.
  2. Subject of either sex, more than 18 years of age

  3. Subjects with moderate to severe overt hyperthyroidism (caused by Graves' disease).

    • Moderate to severe overt hyperthyroidism is defined as Free T4> 1.5 times upper limit of normal reference range and TSH below lower limit of reference range, who are either newly diagnosed or previously diagnosed and receiving ATDs currently.
    • Graves disease is defined as hyperthyroidism coupled with clinical signs of symmetrical diffuse goiter, thyroid orbitopathy, or diffuse and vascular thyroid on ultrasound or positive TRAb antibody

  4. Female patients will either be

    • post-menopausal for > 2 years
    • Women of childbearing potential can be included if surgically sterile or using double contraception with at least one method being barrier contraception. Women of childbearing potential must have a negative pregnancy test at screening and at randomisation. Pregnancy tests will be repeated during each visit.

Exclusion Criteria:

  1. Inability or unwillingness to provide written consent.
  2. Inability or unwillingness to comply with the requirements of the protocol as determined by the investigator.
  3. Pregnancy, breastfeeding or use of non-reliable method of contraception.
  4. Subjects with history of chronic liver disease, chronic renal failure, heart failure, diabetes mellitus
  5. Subjects with history of peptic ulcer disease, upper gastrointestinal bleeding, diverticulitis or ulcerative colitis.
  6. Subjects who have recently had live or attenuated virus vaccines
  7. Subjects with current infection (systemic fungal, active tuberculosis, cerebral malaria, viral hepatitis, HIV)
  8. Subjects with cataracts and glaucoma
  9. Subjects with osteoporosis
  10. Subjects with psychiatric disorders
  11. Subjects with complete biliary obstruction, bleeding disorders, hypertriglyceridemia (fasting triglyceride levels > 300mg/dL)
  12. Previous history of adverse reactions to cholestyramine or other bile acid sequestrants
  13. Previous history of adverse reactions to prednisolone or other steroid compound
  14. Current use of cholestyramine or prednisolone or other steroid compound
  15. Participation in another clinical trial and/or receipt of cholestyramine or prednisolone within 4 weeks prior to screening visit.
  16. Subjects with history of bronchial asthma, bronchospasm, peripheral vascular disease or adverse reactions to propanolol
  17. Subjects with adverse reactions to carbimazole
  18. Hypokalemia (serum K+ <3.5 mmol/L)
  19. Thyroid storm defined as Burch Wartofsky Score >45

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group1:Cholestyramine+standard treatment
Cholestyramine powder 4g twice daily, Tablet Carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks
Drug: Cholestyramine Powder 4g
Cholestyramine powder 4g twice daily, Tablet Carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks
Other Names:
  • Questran
Experimental: Group2:Prednisolone+standard treatment
Tablet prednisolone 30 mg daily for week 1, 20 mg daily for week 2, 10 mg daily for week 3 and 5 mg daily for week 4, Tablet carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks
Drug: Prednisolone
Tablet prednisolone 30 mg daily for week 1, 20 mg daily for week 2, 10 mg daily for week 3 and 5 mg daily for week 4, Tablet carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks
Active Comparator: Group 3: Standard treatment alone
Carbimazole 30 mg daily and propanolol 40 mg twice daily for 4 weeks
Drug: Standard treatment
Carbimazole 30 mg daily and propanolol 40 mg twice daily for 4 weeks
Other Names:
  • Carbimazole + Propanolol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients whose Free T4 normalize between the groups
Time Frame: 4 weeks
Normal Free T4 is defined as Free T4 level between 9-25 pmol/L
4 weeks
Percentage of patients whose Free T3 normalize between the groups
Time Frame: 4 weeks
Normal free T3 is defined as Free T3 level between 3.5-6.5 pmol/L
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events between the groups
Time Frame: 6 weeks
Number of adverse events between the groups
6 weeks
Reduction in Free T4 levels
Time Frame: 4 weeks
Reduction in Free T4 levels ( Change from baseline within 4 weeks)
4 weeks
Reduction in Free T3 levels
Time Frame: 4 weeks
Reduction in Free T3 levels (Change from baseline within 4 weeks)
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Clinical Research Centre, Malaysia

Collaborators

Ministry of Health, Malaysia

Investigators

  • Principal Investigator: Serena SK Khoo, Dr., HospitalPutrajaya

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 11, 2017

Primary Completion (Anticipated)

March 1, 2018

Study Completion (Anticipated)

March 1, 2018

Study Registration Dates

First Submitted

September 13, 2017

First Submitted That Met QC Criteria

October 1, 2017

First Posted (Actual)

October 5, 2017

Study Record Updates

Last Update Posted (Actual)

October 5, 2017

Last Update Submitted That Met QC Criteria

October 1, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ChoPS Study Version 3.0

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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