Adjuvant rituximab, a potential treatment for the young patient with Graves' hyperthyroidism (RiGD): study protocol for a single-arm, single-stage, phase II trial

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Adjuvant rituximab, a potential treatment for the young patient with Graves' hyperthyroidism (RiGD) : study protocol for a single-arm, single-stage, phase II trial. / Cole, Michael; Hynes, Ann Marie; Howel, Denise; Hall, Lesley; Abinun, Mario; Allahabadia, Amit; Barrett, Timothy; Boelaert, Kristien; Drake, Amanda J.; Dimitri, Paul; Kirk, Jeremy; Zammitt, Nicola; Pearce, Simon; Cheetham, Tim.

In: BMJ open, Vol. 9, No. 1, e024705, 21.01.2019.

Research output: Contribution to journalArticle

Harvard

Cole, M, Hynes, AM, Howel, D, Hall, L, Abinun, M, Allahabadia, A, Barrett, T, Boelaert, K, Drake, AJ, Dimitri, P, Kirk, J, Zammitt, N, Pearce, S & Cheetham, T 2019, 'Adjuvant rituximab, a potential treatment for the young patient with Graves' hyperthyroidism (RiGD): study protocol for a single-arm, single-stage, phase II trial', BMJ open, vol. 9, no. 1, e024705. https://doi.org/10.1136/bmjopen-2018-024705

APA

Cole, M., Hynes, A. M., Howel, D., Hall, L., Abinun, M., Allahabadia, A., Barrett, T., Boelaert, K., Drake, A. J., Dimitri, P., Kirk, J., Zammitt, N., Pearce, S., & Cheetham, T. (2019). Adjuvant rituximab, a potential treatment for the young patient with Graves' hyperthyroidism (RiGD): study protocol for a single-arm, single-stage, phase II trial. BMJ open, 9(1), [e024705]. https://doi.org/10.1136/bmjopen-2018-024705

Vancouver

Author

Cole, Michael ; Hynes, Ann Marie ; Howel, Denise ; Hall, Lesley ; Abinun, Mario ; Allahabadia, Amit ; Barrett, Timothy ; Boelaert, Kristien ; Drake, Amanda J. ; Dimitri, Paul ; Kirk, Jeremy ; Zammitt, Nicola ; Pearce, Simon ; Cheetham, Tim. / Adjuvant rituximab, a potential treatment for the young patient with Graves' hyperthyroidism (RiGD) : study protocol for a single-arm, single-stage, phase II trial. In: BMJ open. 2019 ; Vol. 9, No. 1.

Bibtex

@article{19ca8df533bd4604b3b7c00b3fcf8c14,
title = "Adjuvant rituximab, a potential treatment for the young patient with Graves' hyperthyroidism (RiGD): study protocol for a single-arm, single-stage, phase II trial",
abstract = "Introduction Graves' disease (Graves' hyperthyroidism) is a challenging condition for the young person and their family. The excess thyroid hormone generated by autoimmune stimulation of the thyroid stimulating hormone receptor on the thyroid gland can have a profound impact on well-being. Managing the young person with Graves' hyperthyroidism is more difficult than in older people because the side effects of conventional treatment are more significant in this age group and because the disease tends not to resolve spontaneously in the short to medium term. New immunomodulatory agents are available and the anti-B cell monoclonal antibody rituximab is of particular interest because it targets cells that manufacture the antibodies that stimulate the thyroid gland in Graves'. Methods and analysis The trial aims to establish whether the combination of a single dose of rituximab (500 mg) and a 12-month course of antithyroid drug (usually carbimazole) can result in a meaningful increase in the proportion of patients in remission at 2 years, the primary endpoint. A single-stage, phase II A'Hern design is used. 27 patients aged 12-20 years with newly presenting Graves' hyperthyroidism will be recruited. Markers of immune function, including lymphocyte numbers and antibody levels (total and specific), will be collected regularly throughout the trial. Discussion The trial will determine whether the immunomodulatory medication, rituximab, will facilitate remission above and beyond that observed with antithyroid drug alone. A meaningful increase in the expected proportion of young patients entering remission when managed according to the trial protocol will justify consideration of a phase III trial. Ethics and dissemination The trial has received a favourable ethical opinion (North East - Tyne and Wear South Research Ethics Committee, reference 16/NE/0253, EudraCT number 2016-000209-35). The results of this trial will be distributed at international endocrine meetings, in the peer-reviewed literature and via patient support groups. Trial registration number ISRCTN20381716.",
keywords = "clinical trials, immunology, paediatric endocrinology, thyroid disease",
author = "Michael Cole and Hynes, {Ann Marie} and Denise Howel and Lesley Hall and Mario Abinun and Amit Allahabadia and Timothy Barrett and Kristien Boelaert and Drake, {Amanda J.} and Paul Dimitri and Jeremy Kirk and Nicola Zammitt and Simon Pearce and Tim Cheetham",
year = "2019",
month = jan,
day = "21",
doi = "10.1136/bmjopen-2018-024705",
language = "English",
volume = "9",
journal = "BMJ open",
issn = "2044-6055",
publisher = "BMJ Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Adjuvant rituximab, a potential treatment for the young patient with Graves' hyperthyroidism (RiGD)

T2 - study protocol for a single-arm, single-stage, phase II trial

AU - Cole, Michael

AU - Hynes, Ann Marie

AU - Howel, Denise

AU - Hall, Lesley

AU - Abinun, Mario

AU - Allahabadia, Amit

AU - Barrett, Timothy

AU - Boelaert, Kristien

AU - Drake, Amanda J.

AU - Dimitri, Paul

AU - Kirk, Jeremy

AU - Zammitt, Nicola

AU - Pearce, Simon

AU - Cheetham, Tim

PY - 2019/1/21

Y1 - 2019/1/21

N2 - Introduction Graves' disease (Graves' hyperthyroidism) is a challenging condition for the young person and their family. The excess thyroid hormone generated by autoimmune stimulation of the thyroid stimulating hormone receptor on the thyroid gland can have a profound impact on well-being. Managing the young person with Graves' hyperthyroidism is more difficult than in older people because the side effects of conventional treatment are more significant in this age group and because the disease tends not to resolve spontaneously in the short to medium term. New immunomodulatory agents are available and the anti-B cell monoclonal antibody rituximab is of particular interest because it targets cells that manufacture the antibodies that stimulate the thyroid gland in Graves'. Methods and analysis The trial aims to establish whether the combination of a single dose of rituximab (500 mg) and a 12-month course of antithyroid drug (usually carbimazole) can result in a meaningful increase in the proportion of patients in remission at 2 years, the primary endpoint. A single-stage, phase II A'Hern design is used. 27 patients aged 12-20 years with newly presenting Graves' hyperthyroidism will be recruited. Markers of immune function, including lymphocyte numbers and antibody levels (total and specific), will be collected regularly throughout the trial. Discussion The trial will determine whether the immunomodulatory medication, rituximab, will facilitate remission above and beyond that observed with antithyroid drug alone. A meaningful increase in the expected proportion of young patients entering remission when managed according to the trial protocol will justify consideration of a phase III trial. Ethics and dissemination The trial has received a favourable ethical opinion (North East - Tyne and Wear South Research Ethics Committee, reference 16/NE/0253, EudraCT number 2016-000209-35). The results of this trial will be distributed at international endocrine meetings, in the peer-reviewed literature and via patient support groups. Trial registration number ISRCTN20381716.

AB - Introduction Graves' disease (Graves' hyperthyroidism) is a challenging condition for the young person and their family. The excess thyroid hormone generated by autoimmune stimulation of the thyroid stimulating hormone receptor on the thyroid gland can have a profound impact on well-being. Managing the young person with Graves' hyperthyroidism is more difficult than in older people because the side effects of conventional treatment are more significant in this age group and because the disease tends not to resolve spontaneously in the short to medium term. New immunomodulatory agents are available and the anti-B cell monoclonal antibody rituximab is of particular interest because it targets cells that manufacture the antibodies that stimulate the thyroid gland in Graves'. Methods and analysis The trial aims to establish whether the combination of a single dose of rituximab (500 mg) and a 12-month course of antithyroid drug (usually carbimazole) can result in a meaningful increase in the proportion of patients in remission at 2 years, the primary endpoint. A single-stage, phase II A'Hern design is used. 27 patients aged 12-20 years with newly presenting Graves' hyperthyroidism will be recruited. Markers of immune function, including lymphocyte numbers and antibody levels (total and specific), will be collected regularly throughout the trial. Discussion The trial will determine whether the immunomodulatory medication, rituximab, will facilitate remission above and beyond that observed with antithyroid drug alone. A meaningful increase in the expected proportion of young patients entering remission when managed according to the trial protocol will justify consideration of a phase III trial. Ethics and dissemination The trial has received a favourable ethical opinion (North East - Tyne and Wear South Research Ethics Committee, reference 16/NE/0253, EudraCT number 2016-000209-35). The results of this trial will be distributed at international endocrine meetings, in the peer-reviewed literature and via patient support groups. Trial registration number ISRCTN20381716.

KW - clinical trials

KW - immunology

KW - paediatric endocrinology

KW - thyroid disease

UR - http://www.scopus.com/inward/record.url?scp=85060397992&partnerID=8YFLogxK

U2 - 10.1136/bmjopen-2018-024705

DO - 10.1136/bmjopen-2018-024705

M3 - Article

C2 - 30670519

AN - SCOPUS:85060397992

VL - 9

JO - BMJ open

JF - BMJ open

SN - 2044-6055

IS - 1

M1 - e024705

ER -