E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypothyroidism Hypoparathyroidism |
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E.1.1.1 | Medical condition in easily understood language |
Impaired function of the thyroid and parathyroid hands |
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E.1.1.2 | Therapeutic area | Body processes [G] - Cell Physiological Phenomena [G04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Thyroid: We hypothesize that the measurement of tissue concentrations of phosphodiesters (PDEs) employing 31P MRS represents a sensitive and specific tool to quantify peripheral thyroid hormone action and can be applied in clinical practice to optimize thyroid hormone replacement therapy (metabolic virtual biopsy).
Hyper- and Hypoparathyroidism: We propose that the identification of MRS-patterns specific for disorders of calcium metabolism might help to individualize therapeutic decisions in patients with hyper- and hypoparathyroidism. Furthermore, we intend to analyze the time course of MRS-Patterns before and after a single dose of rhPTH 1-84 to determine if PTH per se might have relevant effects on skeletal and heart muscle energy metabolism.
Primary outcome parameter: • 31P MRS pattern in skeletal muscle |
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E.2.2 | Secondary objectives of the trial |
Secondary outcome parameters: 30.04.2021 • Acetylcarnitine levels and ectopic intracellular lipid content in skeletal muscle • Ectopic intracellular lipid content in liver and 31P MRS pattern in the liver (only controls and hypothyroid patients) • Resting energy expenditure • Anthropometric characteristics • Laboratory parameters of thyroid function, i.e. TSH, fT4, fT3, T4, T3, TBG • Laboratory Parameters of Calcium Metabolism, i.e. PTH, Calcium, Kreatinine, Vitamin D, albumin • Laboratory parameters of lipid metabolism, i.e. cholesterol, ldl- and hdl-cholesterol, triglycerides • Laboratory parameters of glucose metabolism, i.e. glucose, insulin, c-peptide, HbA1c • Gender differences • Muscle strength and physical performance • Cardiac function • 31P MRS in Myocardium • Quality of life |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria (subclinical hypothyroidism): (i) TSH > 4μU/ml, fT4 within the reverence range. (ii) Age between 18 and 70 years
Inclusion criteria: (i) Age between 18 and 70 years (ii) Diagnostic criteria fulfilling primary hyperparathyroidism (calcium > 2,5 mmol/l; PTH > upper limit of normal; fractional 24h urinary calcium excretion > 1 %) or hypoparathyroidism (calcium < 2,15 mmol/l; PTH < lower limit of normal)
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E.4 | Principal exclusion criteria |
(i) any known disorder of thyroid function, including subclinical and overt hypo- or hyperthyroidism, (ii) positive thyroid autoantibodies (i.e. TRAK, TG-AK, TPO-AK), (iii) current or previous medication for thyroid disorders, (iv) severe metabolic or liver illness (HbA1c > 8%, Triglycerides > 500 mg/dl, Cholesterol > 300 mg/dl, AST & ALT > 3 x upper limit of normal range) (v) pregnancy (vi) breast feeding (vii) general MR-contraindications, including metal devices or other magnetic material hazardous for MR investigation and claustrophobia (viii) statin therapy |
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E.5 End points |
E.5.1 | Primary end point(s) |
31P MRS pattern in skeletal muscle |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
4-6 and 8-12 weeks after initiation of Levothyroxine substitution
spring 240 min after injection of recombination parathormone |
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E.5.2 | Secondary end point(s) |
Secondary outcome parameters: 30.04.2021 • Acetylcarnitine levels and ectopic intracellular lipid content in skeletal muscle • Ectopic intracellular lipid content in liver and 31P MRS pattern in the liver (only controls and hypothyroid patients) • Resting energy expenditure • Anthropometric characteristics • Laboratory parameters of thyroid function, i.e. TSH, fT4, fT3, T4, T3, TBG • Laboratory Parameters of Calcium Metabolism, i.e. PTH, Calcium, Kreatinine, Vitamin D, albumin • Laboratory parameters of lipid metabolism, i.e. cholesterol, ldl- and hdl-cholesterol, triglycerides • Laboratory parameters of glucose metabolism, i.e. glucose, insulin, c-peptide, HbA1c • Gender differences • Muscle strength and physical performance • Cardiac function • 31P MRS in Myocardium • Quality of life |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
4-6 and 8-12 weeks after initiation of Levothyroxine substitution
spring 240 min after injection of recombination parathormone |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |