Bipolar Disorder MedDRA version: 20.0 Level: LLT Classification code 10004937 Term: Bipolar disorder NEC System Organ Class: 100000004873
Conditions
Interventions
Trade Name: Scopolamine (Hyoscine Hydrobromide)
Product Name: Scopolamine (Hyoscine Hydrobromide)
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Hyoscine Hydrobromide
CAS Nu
Sponsors
National University of ireland Galway
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible each participant must meet all of the following eligibility criteria at Screening (Visit 1) and must continue to fulfil these criteria at Visit 2 to take part in the trial: 1. Diagnosis of Bipolar Disorder according to Diagnostic Statistics Manual (DSM)-V criteria 2. Experiencing an episode of depression of at least moderate severity at Visit 1 (Screening) and Visit 2 based on clinical interview by a trained clinician and a Hamilton Depression Rating Scale (HDRS) score = 14. 3. = 18 years old at Visit 2 (male or female) 4. In the opinion of the Principal Investigator or Sub Investigator’s, be able and willing to provide written informed consent and to comply with the requirements of this study protocol. 5. Written informed consent prior to participating in the study 6. U&Es, LFTs and TFTs laboratory tests within acceptable ranges in the previous 4 months of the Screening Visit (Visit 1). Placebo run-in inclusion criteria at Randomisation visit (Visit 3): 7. In addition to above participants must be experiencing an episode of depression of at least mild severity (having previously experienced an episode of moderate depression at Visit 2 with HDRS = 14), based on clinical interview by a trained clinician and a HDRS score of = 8. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: Participants who meet any one or more of the following exclusion criteria at Screening (Visit 1) or Visit 2 will not be eligible to take part in the trial: 1. History of other Axis I diagnosis (including Recurrent Depressive Disorder or Psychotic Disorders such as schizo-affective disorder, conditions that can also present with depressive episodes) 2. History in the three months prior to Visit 2 of alcohol dependence syndrome or substance dependence syndrome. 3. Current use of oral steroid at Visit 1 4. A confirmed diagnosis of dementia 5. A diagnosis of intellectual disability (IQ 6) at screening or Visit 2. 8. Presence of an established neurological disorder or other serious demyelinating conditions as determined by the treating physician (e.g. space occupying lesion, multiple sclerosis) 9. Current involuntary detention under the Mental Health Act (MHA) 2001 in an acute psychiatric inpatient unit 10. Severity of Bipolar Disorder is such that participation in a clinical trial is not appropriate because of the risk of imminent self-harm (based on clinical note review and review at screening visit by experienced clinician) 11. A history of an allergic reaction or sensitivity to Scopolamine (Hyoscine Hydrobromide). Participants will be asked at the screening visit about any previous treatment with scopolamine (Hyoscine Hydrobromide) to ascertain any previous allergic reaction or sensitivity to this agent. 12. A clinical diagnosis of narrow angle glaucoma, myasthenia gravis, paralytic ileus, pyloric stenosis, toxic megacolon and acute porphyria. 13. Individuals will be excluded from the study if currently prescribed anticholinergic medications including Physostigmine, Biperiden and Procyclidine. Individuals will additionally be excluded if currently prescribed Tricyclic Antidepressants which are associated with significant anticholinergic properties (e.g. Amitriptyline and Nortriptyline) that are currently causing the participant to experience anticholinergic side effects (e.g. blurred vision, constipation, urinary retention, cognitive difficulties). No individuals will have anticholinergic medications stopped to allow them enter the trial. 14. Bradycardia 100bpm or hypotension (systolic BP <90 and / or diastolic BP < 60) prior to IV administration of placebo or Scopolamine 15. A recent history in the last 6 months of symptomatic orthostatic hypotension or syncope. 16. Previous participation in this trial. Participation is defined as randomised. Participation in another trial within 3 months prior to Visit 1. Receipt of any investigational medicinal product (IMP) within 3 months prior to Visit 1. 17. Participants concurrently being administered Electroconvulsive Therapy (ECT). 18. Pregnancy, as determined by a positive urine dipstick at Visits 2, 3, 4, 5, positive blood serum result executed at Visit 2 and confirmed prior to infusion at Visit 3 or participants who are actively breastfeeding (female only). 19. Women of child-bearing potential are defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment. Highly effective contraception methods include: • Female sterilization (have had surgical
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: 1.The primary objective is to investigate the efficacy and safety of IV Scopolamine, compared to placebo, in reducing severity of depression in individuals with bipolar disorder who are experiencing a depressive episode of at least moderate severity. ;Secondary Objective: Secondary objectives: 1.To investigate if IV Scopolamine compared to placebo improves mood, cognition and functioning as measured on a number of objective and subjective psychometric instruments in individuals with bipolar disorder experiencing a depressive episode of at least moderate severity. 2.To investigate the safety and tolerability of repeated (x3) IV Scopolamine versus placebo in individuals with bipolar disorder experiencing a depressive episode of at least moderate severity. ;Primary end point(s): The primary endpoint will be the change in severity of objective depressive symptoms as measured by change in HDRS score from pre-randomisation (pre-IV infusion on Visit 3) compared to Visit 6.;Timepoint(s) of evaluation of this end point: The primary endpoint will be the change in severity of objective depressive symptoms as measured by change in HDRS score from pre-randomisation (pre-IV infusion at Visit 3) compared to Visit 6. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Remission of depressive episode measured with the HDRS at Visit 6 compared to Visit 3. 2. Response to a depressive episode measured with the HDRS at Visit 6 compared to Visit 3. 3. Reduction of depressive symptoms (MADRS) at Visit 6 compared to Visit 3. 4. Improvement in objectively measured overall functioning (GAF) at Visit 6 compared to Visit 3. 5. Reduction in depressive symptoms as measured using the POMS after all IV infusion visits compared to before IV infusions at the same visit (Visits 2, 3, 4, 5). 6. Response and remission data measured with the HDRS at Visit 7 compared to pre-randomisation HDRS scores at Visit 3. 7. Reduction in subjectively measured mood symptoms using the POMS at follow-up visits (Visits 6 and 7) compared to pre-randomisation. 8. Reduction in depressive symptoms, measured with the MADRS at Visit 7 compared to MADRS scores at Visit 3. 9. Improvement in global functioning, measured with the GAF at Visit 7 compared to pre-infusion GAF scores at Visit 3. 10. Psychiatric inpatient admissions due to depressive episodes over the duration of the study. 11. Antidepressant medication usage or change in antidepressant medication dose due to depressive episodes over the duration of the study. 12. Adverse events over the duration of the study. 13. Post infusion side effects at all 3 IV treatment visits: Bradycardia, Hypotension, Dizziness and Sedation (Visits 3, 4 and 5) 14. Occurrence of a hypo (manic) episode over the duration of the study. 15. Improvement in motor processing, visual and spatial memory at Visit 6 compared to initial scores measured at Visit 2 or Visit 3 as measured on CANTAB.;Timepoint(s) of evaluation of this end point: These include change in severity of depressive symptoms at study Visits 3, 4, 5, 6 and 7 and changes in cognitive scores at Visit 6 | — |
Countries
Ireland
Contacts
Public ContactTom Conway
HRB Clinical Research Facility Galway
Outcome results
None listed