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

• Status: Unknown status
• Trial end date: 2018-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Clinical Research Centre, Malaysia
• Collaborator: Ministry of Health, Malaysia
• Treatments: Carbimazole; Cholestyramine Resin; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Propranolol

Criteria

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