NOMOTHETICOS: Nonlinear Modelling of Thyroid Hormones' Effect on Thyrotropin Incretion in Confirmed Open-loop Situation
NCT ID: NCT01145040
Last Updated: 2020-10-08
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
UNKNOWN
138 participants
OBSERVATIONAL
2010-06-01
2021-01-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Phase 4 Study in Secondary Hypothyroidism: Body Weight Adapted Thyroxin Treatment and Triiodothyronine Supplementation
NCT00360074
Novel Approaches to the Treatment of Hypothyroidism
NCT06731764
Desiccated Thyroid Extract Versus Synthetic T3/T4 Combination (ThyrolarTM) Versus L-T4 Alone in the Therapy of Primary Hypothyroidism With Special Attention to the Gene Polymorphism
NCT02317926
Assessing the Impact of the Early and Systematic Hormonal Replacement After Radio-isotopic Ablation of Graves'hyperthyroïdism on Quality of Life, Efficiency and Tolerance
NCT01295333
Randomized Crossover Trial for the Evaluation of the Possible Effects in the Intestine of Two Different Pharmaceutical Forms of L - Thyroxine in Patients With Primary Acquired Hypothyroidism
NCT02917863
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Today, the central component of the thyrotropic feedback control system is still poorly understood on a physiological level. Therefore, in mathematical models different functional relations describing the feedback-inhibition of thyrotropin incretion by thyroid hormones have been suggested \[Danziger and Elmergreen 1956, Roston 1959, Norwich and Reiter 1965, DiStefano and Stear 1968, DiStefano 1969, Saratchandran et al. 1973, Li et al. 1995, Dietrich et al. 2004, Degon et al. 2008, Jonklaas and Soldin 2008, Hörmann et al. 2010\]. Most of these models fail in delivering biochemical explanations for the functional interrelations they postulate.
Nevertheless, some clinical applications of these models have been developed, although their diagnostical potential is usually rather limited \[Yagi et al. 1997, Pohlenz et al. 1999, Jostel et al. 2009\].
Assuming that the pituitary's response to peripheral thyroid hormones is determined by active transmembrane thyroxine transport mechanisms \[Dietrich et al. 2008\], intracellular deiodination of thyroxine (T4), binding of resulting triiodothyronine (T3) to iodothyronine receptors and, finally, their inhibiting effect on mRNA expression, translation and release of TRH, a novel, physiologically motivated model has been developed that is based on compartment-analytical approaches, Michaelis-Menten kinetics and non competitive divisive inhibition \[Dietrich et al 2004\]. However, this model has not been sufficiently evaluated in a clinical context.
It is the aim of the NOMOTHETICOS study to deliver new systems-level insights into the pituitary's thyrotropic function. This unicentric cross-sectional study compares different models of feedback-inhibition by means of modern statistical methods like nonlinear regression and Akaike information criterion. Structural parameters are obtained in vivo from open-loop analysis in patients with disconnected feedback in equilibrium.
These parameters can serve as theoretical basis for possible future trials developing advanced diagnostical evaluation methods of thyrotropic pituitary function.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
COHORT
CROSS_SECTIONAL
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Partition 1
Overt primary hypothyroidism
No interventions assigned to this group
Partition 2
Hypothyroidism with "full dose" levothyroxine substitution therapy (more than 1.75 µg per kg of body mass)
No interventions assigned to this group
Partition 3
Overt primary hyperthyroidism
No interventions assigned to this group
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Overt primary hypothyroidism with TSH level higher than 10 mU/l and FT4 concentration below 7 pmol/L (5.4 ng/L) (Partition 1)
* Overt primary hyperthyroidism with TSH level below 0.1 mU/l and FT4 concentration higher than 18 pmol/L (14 ng/L) (Partition 3)
* All other constellations, if the patient receives substitution therapy with more 1.75 µg Levothyroxin per kg of body mass (Partition 2).
* System in equilibrium (e.g. unchanged substitution dose over the past six weeks)
Exclusion Criteria
* Severe illness that may be associated with euthyroid sick syndrome (non-thyroidal illness syndrome)
* Medication influencing pituitary function
* Pregnancy
* Missing consent for participation in the study
14 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Ruhr University of Bochum
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
PD Dr. Johannes W. Dietrich, MD
Senior consultant endocrinologist
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Johannes W Dietrich, M.D.
Role: PRINCIPAL_INVESTIGATOR
Medical Hospital I, Bergmannsheil University Hospitals, Ruhr University of Bochum
Harald H Klein, M.D.
Role: STUDY_CHAIR
Medical Hospital I, Bergmannsheil University Hospitals, Ruhr University of Bochum
Johannes W Dietrich, M.D.
Role: STUDY_DIRECTOR
Medical Hospital I, Bergmannsheil University Hospitals, Ruhr University of Bochum
Bojana Bazika-Gerasch, M.D.
Role: PRINCIPAL_INVESTIGATOR
Medical Hospital I, Bergmannsheil University Hospitals, Ruhr University of Bochum
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Klinikum Ludwigsburg-Bietigheim
Bietigheim, Baden-Wurttemberg, Germany
Institute for diagnostical radiology, interventional radiology and nuclear medicine, Bergmannsheil University Hospitals, Ruhr University of Bochum
Bochum, North Rhine-Westphalia, Germany
Medical Hospital I, Bergmannsheil University Hospitals, Ruhr University of Bochum
Bochum, North Rhine-Westphalia, Germany
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Norwich KH, Reiter R. Homeostatic control of thyroxin concentration expressed by a set of linear differential equations. Bull Math Biophys. 1965 Jun;27(2):133-44. doi: 10.1007/BF02498768. No abstract available.
DiStefano JJ 3rd, Stear EB. Neuroendocrine control of thyroid secretion in living systems: a feedback control system model. Bull Math Biophys. 1968 Mar;30(1):3-26. doi: 10.1007/BF02476936. No abstract available.
DiStefano JJ 3rd. A model of the normal thyroid hormone glandular secretion mechanism. J Theor Biol. 1969 Mar;22(3):412-7. doi: 10.1016/0022-5193(69)90013-7. No abstract available.
Saratchandran P, Carson ER, Reeve J. An improved mathematical model of human thyroid hormone regulation. Clin Endocrinol (Oxf). 1976 Sep;5(5):473-83. doi: 10.1111/j.1365-2265.1976.tb01976.x.
Li G, Liu B, Liu Y. A dynamical model of the pulsatile secretion of the hypothalamo-pituitary-thyroid axis. Biosystems. 1995;35(1):83-92. doi: 10.1016/0303-2647(94)01484-o.
Degon M, Chipkin SR, Hollot CV, Zoeller RT, Chait Y. A computational model of the human thyroid. Math Biosci. 2008 Mar;212(1):22-53. doi: 10.1016/j.mbs.2007.10.009. Epub 2007 Nov 6.
Dietrich JW, Brisseau K, Boehm BO. [Absorption, transport and bio-availability of iodothyronines]. Dtsch Med Wochenschr. 2008 Aug;133(31-32):1644-8. doi: 10.1055/s-0028-1082780. German.
Yagi H, Pohlenz J, Hayashi Y, Sakurai A, Refetoff S. Resistance to thyroid hormone caused by two mutant thyroid hormone receptors beta, R243Q and R243W, with marked impairment of function that cannot be explained by altered in vitro 3,5,3'-triiodothyroinine binding affinity. J Clin Endocrinol Metab. 1997 May;82(5):1608-14. doi: 10.1210/jcem.82.5.3945.
Pohlenz J, Weiss RE, Macchia PE, Pannain S, Lau IT, Ho H, Refetoff S. Five new families with resistance to thyroid hormone not caused by mutations in the thyroid hormone receptor beta gene. J Clin Endocrinol Metab. 1999 Nov;84(11):3919-28. doi: 10.1210/jcem.84.11.6080.
Jostel A, Ryder WD, Shalet SM. The use of thyroid function tests in the diagnosis of hypopituitarism: definition and evaluation of the TSH Index. Clin Endocrinol (Oxf). 2009 Oct;71(4):529-34. doi: 10.1111/j.1365-2265.2009.03534.x. Epub 2009 Feb 18.
Jonklaas J, Soldin SJ. Tandem mass spectrometry as a novel tool for elucidating pituitary-thyroid relationships. Thyroid. 2008 Dec;18(12):1303-11. doi: 10.1089/thy.2008.0155.
Danziger L, Elmergreen GL. The Thyroid-Pituitary Homeostatic Mechanism. Bulletin of Mathematical Biophysics 18 : 1-13, 1956.
Roston S: Mathematical Represention of Some Endocrinological Systems. Bulletin of Mathematical Biophysics, 21:271-282, 1959.
Dietrich JW,Tesche A, Pickardt, CR, Mitzdorf U. Thyrotropic Feedback Control: Evidence for an Additional Ultrashort Feedback Loop from Fractal Analysis. Cybernetics and Systems 35 (4): 315-31, 2004.
Hoermann R, Eckl W, Hoermann C, Larisch R. Complex relationship between free thyroxine and TSH in the regulation of thyroid function. Eur J Endocrinol. 2010 Jun;162(6):1123-9. doi: 10.1530/EJE-10-0106. Epub 2010 Mar 18.
Dietrich JW, Landgrafe G, Fotiadou EH. TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis. J Thyroid Res. 2012;2012:351864. doi: 10.1155/2012/351864. Epub 2012 Dec 30.
Dietrich JW, Leow MK, Goede SL, Midgley JE, Landgrafe G, Hoermann R. Do thyroid-stimulating hormone, body weight, or body mass index serve as adequate markers to guide levothyroxine dose titration? J Am Coll Surg. 2013 Oct;217(4):752-3. doi: 10.1016/j.jamcollsurg.2013.06.008. No abstract available.
Dietrich JW, Landgrafe-Mende G, Wiora E, Chatzitomaris A, Klein HH, Midgley JE, Hoermann R. Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research. Front Endocrinol (Lausanne). 2016 Jun 9;7:57. doi: 10.3389/fendo.2016.00057. eCollection 2016.
Dietrich JW, Midgley JEM, Hoermann R. Editorial: "Homeostasis and Allostasis of Thyroid Function". Front Endocrinol (Lausanne). 2018 Jun 5;9:287. doi: 10.3389/fendo.2018.00287. eCollection 2018. No abstract available.
Berberich J, Dietrich JW, Hoermann R, Muller MA. Mathematical Modeling of the Pituitary-Thyroid Feedback Loop: Role of a TSH-T3-Shunt and Sensitivity Analysis. Front Endocrinol (Lausanne). 2018 Mar 21;9:91. doi: 10.3389/fendo.2018.00091. eCollection 2018.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
3718-10
Identifier Type: OTHER
Identifier Source: secondary_id
U1111-1122-3273
Identifier Type: REGISTRY
Identifier Source: secondary_id
DRKS00003153
Identifier Type: REGISTRY
Identifier Source: secondary_id
TFC-UK10
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.