AzTrials
AzTrials

HyperthyroidismPhase 3ChoPSNCT03303053

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

A Phase 3 study testing Cholestyramine Powder 4g, Prednisolone and Standard treatment in people with Hyperthyroidism and Graves Disease, run by Clinical Research Centre, Malaysia at 3 sites in Malaysia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hyperthyroidism, Graves Disease
What is being tested?
Cholestyramine Powder 4g, Prednisolone and Standard treatment
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
135 participants
Where
3 sitesMalaysia
Study dates
11 May 2017to 1 Mar 2018
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 19Show fewer
  • 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

Trial locations and contacts

3 sites in 1 country.

Serena SK Khoo, Dr. contact

+603 83124200

sk_liv@rocketmail.com

Zanariah Hussein, Dr. contact

+03 83124200

zanariahh@hotmail.com

Malaysia3 sites, 3 recruiting

  • Hospital Ampang

    Ampang, Selangor, 68000

    Vijiya M Valayatham, Dr, +60342896000, ammu_vj@yahoo.com

    Recruiting

  • Hospital Queen Elizabeth 2

    Kota Kinabalu, Sabah, 88300

    Yin Khet Fung, Dr., +6 088324600, fung@doctors.org.uk

    Gayathri D Krishnan, Dr., +6 088324600, kgaya3@yahoo.com

    Recruiting

  • Hospital Putrajaya

    Putrajaya, Kuala Lumpur, 62250

    Serena SK Khoo, Dr., +6 03 83124200, sk_liv@rocketmail.com

    Zanariah Hussein, Dr., +6 03 83124200, zanariahh@hotmail.com

    Recruiting

Other trials in Malaysia

About this study

Official title: 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.

Read the 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.

Being tested
Cholestyramine Powder 4g, Prednisolone, Standard treatment
Keywords
Hyperthyroidism,Graves disease,Cholestyramine,Prednisolone
Medical subject headings
Hyperthyroidism, Graves Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cholestyramine Powder 4gDrug

    Also called Questran

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

  • PrednisoloneDrug

    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

  • Standard treatmentDrug

    Also called Carbimazole + Propanolol

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

Study groups in NCT03303053
Study groupRoleWhat they receive
Group1:Cholestyramine+standard treatmentExperimentalCholestyramine powder 4g twice daily, Tablet Carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks
Receives: Drug: Cholestyramine Powder 4g
Group2:Prednisolone+standard treatmentExperimentalTablet 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
Receives: Drug: Prednisolone
Group 3: Standard treatment aloneActive comparatorCarbimazole 30 mg daily and propanolol 40 mg twice daily for 4 weeks
Receives: Drug: Standard treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of patients whose Free T4 normalize between the groups

    Normal Free T4 is defined as Free T4 level between 9-25 pmol/L

    Measured: 4 weeks

  2. 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

    Measured: 4 weeks

Secondary outcomes (3)

  1. Adverse events between the groups

    Number of adverse events between the groups

    Measured: 6 weeks

  2. Reduction in Free T4 levels

    Reduction in Free T4 levels ( Change from baseline within 4 weeks)

    Measured: 4 weeks

  3. Reduction in Free T3 levels

    Reduction in Free T3 levels (Change from baseline within 4 weeks)

    Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Oct 2017
  2. Study start11 May 2017
  3. Primary completion1 Mar 2018 (estimated)
  4. Study completion1 Mar 2018 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Multi-center, open label, randomised, parallel-group
Masking
None (open label)
Enrolment
135 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03303053
Sponsor's protocol ID
ChoPS Study Version 3.0
Acronym
ChoPS
Status last verified
Oct 2017
First submitted
13 Sep 2017
Last updated
5 Oct 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 17389704

  • 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.

    PubMed 11836274

  • 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.

    PubMed 24423323

  • 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.

    PubMed 27521067

  • 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.

    PubMed 18752767

  • 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.

    PubMed 15302638

  • 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.

    PubMed 23824415

  • 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.

    PubMed 18946743

  • 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.

    PubMed 15850146

  • 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.

    PubMed 8435884

  • 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.

    PubMed 8784067

  • 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.

    PubMed 8796215

  • 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.

    PubMed 1814659

  • 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.

    PubMed 8977745

  • 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.

    PubMed 6688394

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cholestyramine Powder 4g, Prednisolone and Standard treatment in people with Hyperthyroidism and Graves Disease, run by Clinical Research Centre, Malaysia at 3 sites in Malaysia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 5 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Malaysia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Serena SK Khoo, Dr. (+603 83124200, sk_liv@rocketmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of patients whose Free T4 normalize between the groups (time frame: 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03303053, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in