depression unipolar depressive disorder
Conditions
Interventions
None listed
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Age of 18-45 years (extremes included); Able and willing to sign the Informed Consent Form prior to screening evaluations; Able to refrain from use of all (methyl)xanthines (e.g. coffee, tea, cola, chocolate) from admission at 22h00 prior to each study day and during each stay at the CHDR clinic; Able to refrain from alcohol use from 24 hours prior to and for the duration of every stay at the CHDR clinic; Able to refrain from strenuous physical exercise from 48-hours prior to each dosing until dismissal from the CHDR clinic; No disturbed day/night rhythm due to e.g. working in night-shifts or traveling over time zones within 3 weeks prior to the first dose; Use of no prescribed drug (especially psychotropic drugs) within two weeks preceding the first dose, excluding paracetamol and certain dermatological preparations (as to judgement of research physician); Using a current daily average of less than 4 Units alcohol, or maximally consuming less than 6 U alcohol per occasion of alcohol use; Using a current daily average of less than 4 Units (methyl)xanthines (e.g. coffee, tea, cola, chocolate); Smoking less than 5 cigarettes per day; No past or present recreational use of methamphetamines, MDMA or *ecstasy*; No history of drug sensitivity.
Exclusion criteria
Exclusion criteria: A body mass index (BMI) of less than 18 or more than 28 (extremes included) and a body weight of less than 60 kg; (History of) physical and mental illness as determined by history taking, physical and laboratory examinations, ECG and vital signs recordings; Clinically significant pulmonary, cardiac, renal, hepatic, neurological (including epilepsy), endocrinological or gastrointestinal disease; History of movement disorder (including movement disorder due to D-antagonists); Past or present clinically significant DSM-IV psychiatric disorder and/or substance abuse disorder, as diagnosed by GP or psychiatrist; Parents, children or siblings with a psychiatric disease as diagnosed by GP or psychiatrist; Use of illicit drugs within two weeks prior to screening; Positive drug (morphine, benzodiazepines, cocaine, amphetamine, THC, metamphetamines, MDMA) or alcohol screen at screening and or/admission; Blood donation within 90 days prior to the first dose; Participation in an investigational drug study within 90 days prior to the first dose, or in four studies (or more) in the past year; Positive test result on hepatitis B surface antigen or hepatitis C antibodies; Positive test result on HIV 1/2 serology
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacodynamic parameters: 1. plasma ACTH; 2. plasma total and free cortisol 3. saliva cortisol; 4. plasma vasopressin; 5. serum prolactin; 6. Symptom Check List, somatization subscale (SCL-90-SOM); 7. Bond and Lader Visual Analogue Scales (VAS) for alertness, mood, calmness and nausea. Pharmacokinetic parameters: 1. plasma metoclopramide; 2. plasma 5-HTP. Endpoints of the study Primary study endpoints 1. Effect of metoclopramide on plasma AVP release and neuroendocrine response of cortisol and ACTH (average time profiles) in the absence of the 5-HTP-challenge. 2. Effect of metoclopramide on plasma AVP release and neuroendocrine response of cortisol and ACTH (average time profiles) in the presence of the 5-HTP-challenge. 3. Effect of MCP combined with the 5-HTP challenge versus the combined effects of the separate 5-HTP and MCP challenge (average time profiles). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary study endpoints: 1. Effect MCP on the release on the release of plasma prolactin in the presence and absence of the 5-HTP challenge (time profiles, AUC*s). 2. Effect on release of plasma AVP by 5-HTP challenge (time profiles, AUC*s). 3. Effects of MCP, 5-HTP/CBD/granisetron, 5-HTP/CBD/granisetron and MCP on plasma AVP release. 4. Concentration-effect relationships for AVP, ACTH, prolactin, serum cortisol, saliva cortisol for MCP, 5-HTP/CBD/granisetron, 5-HTP/CBD/granisetron and MCP respectively. 5. PK-PD of metoclopramide. | — |
Countries
Netherlands
Outcome results
None listed