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

NCT03303053 | Unknown Phase 3

• 1 other identifier: ChoPS Study Version 3.0
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Hyperthyroidism; Graves Disease

Keywords

Hyperthyroidism,Graves disease,Cholestyramine,Prednisolone

Outcome Measures

Primary Outcomes (2)

• Percentage of patients whose Free T4 normalize between the groups

  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

  Normal free T3 is defined as Free T3 level between 3.5-6.5 pmol/L

  4 weeks

Secondary Outcomes (3)

• Adverse events between the groups

  6 weeks

• Reduction in Free T4 levels

  4 weeks

• Reduction in Free T3 levels

  4 weeks

Study Arms (3)

Group1:Cholestyramine+standard treatment

EXPERIMENTAL

Cholestyramine powder 4g twice daily, Tablet Carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks

Drug: Cholestyramine Powder 4g

Group2:Prednisolone+standard treatment

EXPERIMENTAL

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

Group 3: Standard treatment alone

ACTIVE COMPARATOR

Carbimazole 30 mg daily and propanolol 40 mg twice daily for 4 weeks

Drug: Standard treatment

Interventions

Cholestyramine Powder 4g DRUG

Cholestyramine powder 4g twice daily, Tablet Carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks

Also known as: Questran

Group1:Cholestyramine+standard treatment

Prednisolone DRUG

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

Group2:Prednisolone+standard treatment

Standard treatment DRUG

Carbimazole 30 mg daily and propanolol 40 mg twice daily for 4 weeks

Also known as: Carbimazole + Propanolol

Group 3: Standard treatment alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Clinical Research Centre, Malaysia: lead
• Ministry of Health, Malaysia: collaborator

Study Sites (3)

Hospital Putrajaya

Putrajaya, Kuala Lumpur, 62250, Malaysia

RECRUITING

Hospital Queen Elizabeth 2

Kota Kinabalu, Sabah, 88300, Malaysia

RECRUITING

Hospital Ampang

Ampang, Selangor, 68000, Malaysia

RECRUITING

Related Publications (16)

• Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, Hamada N. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease. J Clin Endocrinol Metab. 2007 Jun;92(6):2157-62. doi: 10.1210/jc.2006-2135. Epub 2007 Mar 27.

  PMID: 17389704 BACKGROUND

• Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002 Feb;87(2):489-99. doi: 10.1210/jcem.87.2.8182.

  PMID: 11836274 BACKGROUND

• Garmendia Madariaga A, Santos Palacios S, Guillen-Grima F, Galofre JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab. 2014 Mar;99(3):923-31. doi: 10.1210/jc.2013-2409. Epub 2014 Jan 1.

  PMID: 24423323 BACKGROUND

• Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, Rivkees SA, Samuels M, Sosa JA, Stan MN, Walter MA. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016 Oct;26(10):1343-1421. doi: 10.1089/thy.2016.0229.

  PMID: 27521067 BACKGROUND

• Dahl P, Danzi S, Klein I. Thyrotoxic cardiac disease. Curr Heart Fail Rep. 2008 Sep;5(3):170-6. doi: 10.1007/s11897-008-0026-9.

  PMID: 18752767 BACKGROUND

• Frost L, Vestergaard P, Mosekilde L. Hyperthyroidism and risk of atrial fibrillation or flutter: a population-based study. Arch Intern Med. 2004 Aug 9-23;164(15):1675-8. doi: 10.1001/archinte.164.15.1675.

  PMID: 15302638 BACKGROUND

• Sundaresh V, Brito JP, Wang Z, Prokop LJ, Stan MN, Murad MH, Bahn RS. Comparative effectiveness of therapies for Graves' hyperthyroidism: a systematic review and network meta-analysis. J Clin Endocrinol Metab. 2013 Sep;98(9):3671-7. doi: 10.1210/jc.2013-1954. Epub 2013 Jul 3.

  PMID: 23824415 BACKGROUND

• Kaykhaei MA, Shams M, Sadegholvad A, Dabbaghmanesh MH, Omrani GR. Low doses of cholestyramine in the treatment of hyperthyroidism. Endocrine. 2008 Aug-Dec;34(1-3):52-5. doi: 10.1007/s12020-008-9107-5. Epub 2008 Oct 23.

  PMID: 18946743 BACKGROUND

• Migneco A, Ojetti V, Testa A, De Lorenzo A, Gentiloni Silveri N. Management of thyrotoxic crisis. Eur Rev Med Pharmacol Sci. 2005 Jan-Feb;9(1):69-74.

  PMID: 15850146 BACKGROUND

• Solomon BL, Wartofsky L, Burman KD. Adjunctive cholestyramine therapy for thyrotoxicosis. Clin Endocrinol (Oxf). 1993 Jan;38(1):39-43. doi: 10.1111/j.1365-2265.1993.tb00970.x.

  PMID: 8435884 BACKGROUND

• Mercado M, Mendoza-Zubieta V, Bautista-Osorio R, Espinoza-de los Monteros AL. Treatment of hyperthyroidism with a combination of methimazole and cholestyramine. J Clin Endocrinol Metab. 1996 Sep;81(9):3191-3. doi: 10.1210/jcem.81.9.8784067.

  PMID: 8784067 BACKGROUND

• Jude EB, Dale J, Kumar S, Dodson PM. Treatment of thyrotoxicosis resistant to carbimazole with corticosteroids. Postgrad Med J. 1996 Aug;72(850):489-91. doi: 10.1136/pgmj.72.850.489.

  PMID: 8796215 BACKGROUND

• Baeza A, Aguayo J, Barria M, Pineda G. Rapid preoperative preparation in hyperthyroidism. Clin Endocrinol (Oxf). 1991 Nov;35(5):439-42. doi: 10.1111/j.1365-2265.1991.tb03562.x.

  PMID: 1814659 BACKGROUND

• Page SR, Sheard CE, Herbert M, Hopton M, Jeffcoate WJ. A comparison of 20 or 40 mg per day of carbimazole in the initial treatment of hyperthyroidism. Clin Endocrinol (Oxf). 1996 Nov;45(5):511-6. doi: 10.1046/j.1365-2265.1996.00800.x.

  PMID: 8977745 BACKGROUND

• Ozawa Y, Daida H, Shimizu T, Shishiba Y. Rapid improvement of thyroid function by using glucocorticoid indicated for the preoperative preparation of subtotal thyroidectomy in Graves' disease. Endocrinol Jpn. 1983 Feb;30(1):93-100. doi: 10.1507/endocrj1954.30.93.

  PMID: 6688394 BACKGROUND

• Conn HO, Poynard T. Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy. J Intern Med. 1994 Dec;236(6):619-32. doi: 10.1111/j.1365-2796.1994.tb00855.x.

  PMID: 7989897 BACKGROUND

MeSH Terms

Conditions

Hyperthyroidism; Graves Disease

Interventions

Cholestyramine Resin; Prednisolone; Carbimazole; Propranolol

Condition Hierarchy (Ancestors)

Thyroid Diseases; Endocrine System Diseases; Exophthalmos; Orbital Diseases; Eye Diseases; Goiter; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Polystyrenes; Plastics; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Serena SK Khoo, Dr.

  HospitalPutrajaya

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Serena SK Khoo, Dr.

CONTACT

+603 83124200; sk_liv@rocketmail.com

Zanariah Hussein, Dr.

CONTACT

+03 83124200; zanariahh@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-center, open label, randomised, parallel-group

Study Record Dates

• First Submitted: September 13, 2017
• First Posted: October 5, 2017
• Study Start: May 11, 2017
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: October 5, 2017

Record last verified: 2017-10

Locations

MY (3)