E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Anorexia Nervosa and Healthy Controls |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To study the effects of thiamine on weight in Anorexia Nervosa and controls and the tolerability of thiamine treatment. |
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E.2.2 | Secondary objectives of the trial |
a) To study if addition of thiamine treatment has beneficial neurocognitive effects in patients with Anorexia Nervosa.
b) To study thiamine status in patients with Anorexia Nervosa at inclusion to study, and after six weeks of treatment.
c) An explorative study of biochemical and genetic markers in relation to Anorexia Nervosa, with a special focus on mitochondrial DNA and factors related to thiamine regulation of glucose metabolism.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Male or female, 18-65 years of age, who has given written con-sent for his/her participation to the study¸ Women of Childbearing Capacity (WOCBC) only if willing to comply with effective contra-ception methods during the course of the trial. Acceptable methods are such as oral contraceptives, contraceptive patches, contracep-tive implant, vaginal contraceptive, double-barrier methods (for example, condom and spermicide), intrauterine device (IUD), hor-monal IUD
2) A diagnosis of Anorexia Nervosa. An age of 18 or older. A verified duration of symptoms of at least 3 months. A minimum BMI of 13 and a BMI less than 19. A written consent to participate in the study and to adhere to the study protocol, a willingness to start treatment as usual and to receive three intramuscular injections of 100mg thiamine.
3) Normal-weight Controls. An age of 18 or older. No current severe somatic or psychiatric illness. A written consent to participate in the study and to adhere to the study protocol and a willingness to receive three intramuscular injections with thiamine.
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E.4 | Principal exclusion criteria |
1) Short life expectancy due to other comorbidity
2) Contraindication for or otherwise not compliant with the thiamine injections or other investigations
3) Documented allergy or intolerance to study drug
4) Severe psychiatric condition or other reason that jeopardize compliance with follow up.
5) On fertile females, pregnancy assessed by anamnesis and pregnancy test
6) Current high-dose treatment with thiamine, or recent (within the last month), high-dose treatment with thiamine.
7) Current diagnosis of alcoholism, drug abuse or mental retardation. A current prescription of atypical neuroleptics or benzodiaz-epines. Positive drug screening.
7) Current diagnosis of alcoholism, drug abuse or mental retardation. A current prescription of atypical neurolep-tics or benzodiazepines. Positive drug-screening.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is to evaluate the treatment-effect of thiamine in Anorexia Nervosa. The main outcome is weight-gain, as measured by increase in kilograms, which is a fairly standard way of evaluating the efficacy of treatment for anorexia. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Weight-gain recorded closest to day 42 of treatment. |
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E.5.2 | Secondary end point(s) |
a) Change in appetite. Based on scores on the “appetite”-item in MADRS-s, at start of study and after 6 weeks.
b) Change in mood and anxiety, as measured by total MADRS-s-score at inclusion to study and after 6 weeks.
c) Change in neurocognitive function, with a specific focus on learning and memory.
d) Thiamine levels and thiamine metabolism in patients having been treated for Anorexia Nervosa. Measure-ments of serum thiamine levels and transketolase-activity at inclusion and after 6 weeks.
e) Epigenetic effects of treatment with thiamine and treatment-as-usual for Anorexia Nervosa. Analysis of DNA and mitochondrial DNA associated with the uptake and function of thiamine.
f) Effects of treatment on lipids, cortisol and oxysterols.
g) Compliance to treatment
o Adverse events
o Compliance to drug prescription
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) At start of study and after 6 weeks.
b) At inclusion to study and after 6 weeks.
c) At inclusion to study and after 6 weeks.
d) At inclusion to study and after 6 weeks.
e) At inclusion to study.
f) At inclusion to study and after 6 weeks
g) From the time a patient receives the first injection until up to 30 day follow-up period after completion of the trial |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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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The study will be formally closed when 15 patients and 15 controls have been recruited and completed the study, or 2 years after recruitment has started, whichever comes first. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |