Efficacy and Safety of Cholestyramine and Prednisolone as Adjunctive Therapy in Treatment of Overt Hyperthyroidism (ChoPS)
Hyperthyroidism, Graves Disease
About this trial
This is an interventional treatment trial for Hyperthyroidism focused on measuring Hyperthyroidism,Graves disease,Cholestyramine,Prednisolone
Eligibility Criteria
Inclusion Criteria:
- Provision of written consent by subject or guardian.
- Subject of either sex, more than 18 years of age
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
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:
- Inability or unwillingness to provide written consent.
- Inability or unwillingness to comply with the requirements of the protocol as determined by the investigator.
- Pregnancy, breastfeeding or use of non-reliable method of contraception.
- Subjects with history of chronic liver disease, chronic renal failure, heart failure, diabetes mellitus
- Subjects with history of peptic ulcer disease, upper gastrointestinal bleeding, diverticulitis or ulcerative colitis.
- Subjects who have recently had live or attenuated virus vaccines
- Subjects with current infection (systemic fungal, active tuberculosis, cerebral malaria, viral hepatitis, HIV)
- Subjects with cataracts and glaucoma
- Subjects with osteoporosis
- Subjects with psychiatric disorders
- Subjects with complete biliary obstruction, bleeding disorders, hypertriglyceridemia (fasting triglyceride levels > 300mg/dL)
- Previous history of adverse reactions to cholestyramine or other bile acid sequestrants
- Previous history of adverse reactions to prednisolone or other steroid compound
- Current use of cholestyramine or prednisolone or other steroid compound
- Participation in another clinical trial and/or receipt of cholestyramine or prednisolone within 4 weeks prior to screening visit.
- Subjects with history of bronchial asthma, bronchospasm, peripheral vascular disease or adverse reactions to propanolol
- Subjects with adverse reactions to carbimazole
- Hypokalemia (serum K+ <3.5 mmol/L)
- Thyroid storm defined as Burch Wartofsky Score >45
Sites / Locations
- Hospital Queen Elizabeth 2Recruiting
- Hospital AmpangRecruiting
- Hospital PutrajayaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
Group1:Cholestyramine+standard treatment
Group2:Prednisolone+standard treatment
Group 3: Standard treatment alone
Cholestyramine powder 4g twice daily, Tablet Carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks
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
Carbimazole 30 mg daily and propanolol 40 mg twice daily for 4 weeks