Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000486628
Ethics application status
Approved
Date submitted
1/05/2023
Date registered
12/05/2023
Date last updated
14/06/2024
Date data sharing statement initially provided
12/05/2023
Date results information initially provided
14/06/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessing the effects of Lysergic acid diethylamide (LSD) microdosing in people experiencing depression (LSDDEP1)
Scientific title
An open-label pilot trial assessing tolerability and feasibility of LSD microdosing in patients with major depressive disorder (LSDDEP1).
Secondary ID [1] 309475 0
None
Universal Trial Number (UTN)
Trial acronym
LSDDEP1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
major depressive disorder 329737 0
Condition category
Condition code
Mental Health 326636 326636 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Sublingually administered Lysergic acid diethylamide (LSD) solution.
Two doses taken every week for eight weeks.
Starting dose is 8 mcg on a pre-defined titration schedule. The dose will be increased by 1 mcg each time and reduced by 3 mcg if participants do not find the new dose tolerable. Titration limits are 5-15 mcg.
Adherence will be monitored by participants sending video recordings of each dose administration to the study team
Intervention code [1] 325898 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 334608 0
Percentage of participants completing the dosing regimen determined by audit of study case report files.
Timepoint [1] 334608 0
At the conclusion of study
Primary outcome [2] 334609 0
Percentage of attended clinic visits once enrolled determined by audit of study case report files.
Timepoint [2] 334609 0
At the conclusion of study
Secondary outcome [1] 421398 0
Total score of the Montomery-Asberg Depressive Rating Scale (MADRS)
Timepoint [1] 421398 0
8 weeks post-commencement of the intervention. Additional assessments are made at baseline (pre-commencement), 2 weeks, 4 weeks and 6 weeks post-commencement of intervention

Eligibility
Key inclusion criteria
1. Provision of signed and dated informed consent form.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Any gender identity aged, 21-65 years .
4. Diagnosis of Major Depressive Disorder (MDD) as per the DSM-5 criteria for MDD
5. Have a MADRS score between 18-35 at the time of screening.
6. Ability to take oral medication and be willing to adhere to the study intervention regimen.
7. For persons of child-bearing potential: agree to use an effective or highly effective contraception
Minimum age
21 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Current or past history schizophrenia or other psychotic disorders, or bipolar I or II disorder
2. Diagnosis of PTSD as assessed by clinical interview
3. Diagnosis of an eating disorder as assessed by clinical interview
4. Risk of suicide as determined by The Columbia-Suicide Severity Rating Scale (C-SSRS).
5. Substance dependence in the previous 6 months
6. Problematic use of alcohol defined as a score on the AUDIT of 16 or greater.
7. Stage II or higher treatment-resistant depression as defined by the Thase and Rush (1997)
staging criteria for the current depressive episode.
8. BMI <18 and > 35.
9. Planned or current pregnancy or lactation.
10. Cardiovascular conditions including abnormal heart rate or blood pressure
11. Significant renal or hepatic impairment.
12. Abnormal 12-lead ECG as judged by a study physician.
13. Abnormal laboratory test findings as judged by a study physician.
14. Use of monoamine oxidase inhibitors, methylphenidate or dexamphetamine.
15. Excessive on-going medication burden as determined by a study physician.
16. Any lifetime history of psychedelic microdosing.
17. Use of serotonergic psychedelic drugs in the last year.
18. Lifetime history of self-medicating with psychedelics to treat their depression.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
27/06/2023
Actual
14/08/2023
Date of last participant enrolment
Anticipated
3/06/2024
Actual
18/12/2023
Date of last data collection
Anticipated
8/08/2024
Actual
18/04/2024
Sample size
Target
20
Accrual to date
Final
20
Recruitment outside Australia
Country [1] 25420 0
New Zealand
State/province [1] 25420 0

Funding & Sponsors
Funding source category [1] 313672 0
Government body
Name [1] 313672 0
Health Reseach Council of New Zealand
Country [1] 313672 0
New Zealand
Funding source category [2] 313745 0
Commercial sector/Industry
Name [2] 313745 0
MindBio Therapeutics Ltd
Country [2] 313745 0
Australia
Primary sponsor type
University
Name
The University of Auckland
Address
University of Auckland
Private Bag 92019
Auckland 1142
New Zealand
Country
New Zealand
Secondary sponsor category [1] 315562 0
None
Name [1] 315562 0
Address [1] 315562 0
Country [1] 315562 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312837 0
Southern HDEC
Ethics committee address [1] 312837 0
Health and Disability Ethics Committees Ministry of Health 133 Molesworth Street PO Box 5013 Wellington 6011
Ethics committee country [1] 312837 0
New Zealand
Date submitted for ethics approval [1] 312837 0
Approval date [1] 312837 0
14/12/2022
Ethics approval number [1] 312837 0

Summary
Brief summary
Depressive disorders are the leading cause of “years lived with disability” in New Zealand and there is a clear need for the development of new, alternative antidepressant therapies. In light of problems with the tolerability and efficacy of available treatments, a global trend is emerging for patients to self-treat depression with microdoses of psychedelic drugs such as lysergic acid diethylamide (LSD) and psilocybin. Beyond anecdotal reports from those who self-medicate in this way, there are few clinical trials that have evaluated this practice. In our recently published Phase 1 study in healthy volunteers (https://pubmed.ncbi.nlm.nih.gov/36997080/; ACTRN12621000436875) , we determined that LSD microdosing was relatively safe in this cohort and well-tolerated. Further the data demonstrate that conducting such microdosing studies is feasible with excellent adherence and compliance to regimen observed. In this open-label pilot trial with patients with major depressive disorder (MDD) we will test the tolerability and feasibility of an 8 week regimen of LSD microdosing in this patient group.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126090 0
A/Prof Suresh Muthukumaraswamy
Address 126090 0
School of Pharmacy The University of Auckland Private Bag 92019 Auckland 1142
Country 126090 0
New Zealand
Phone 126090 0
+64 093737599
Fax 126090 0
Email 126090 0
[email protected]
Contact person for public queries
Name 126091 0
A/Prof Suresh Muthukumaraswamy
Address 126091 0
School of Pharmacy The University of Auckland Private Bag 92019 Auckland 1142
Country 126091 0
New Zealand
Phone 126091 0
+64 093737599
Fax 126091 0
Email 126091 0
[email protected]
Contact person for scientific queries
Name 126092 0
A/Prof Suresh Muthukumaraswamy
Address 126092 0
School of Pharmacy The University of Auckland Private Bag 92019 Auckland 1142
Country 126092 0
New Zealand
Phone 126092 0
+64 093737599
Fax 126092 0
Email 126092 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Commercial sensitivity


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.