Major Depressive DisorderPhase 1NCT05553691
SPL026 With or Without SSRIs in Participants With MDD
A Phase 1 study testing SPL026 in people with Major Depressive Disorder, run by Small Pharma Ltd at 2 sites in United Kingdom.
Trial summary
The main aim of the study is to test the safety and tolerability of single doses of SPL026 (N,N-dimethyltryptamine [DMT] fumarate, a psychedelic tryptamine) in patients currently taking a selective serotonin reuptake inhibitor (SSRI) for their depression, but for whom the SSRI is not fully relieving their depression. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- SPL026
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 13 Dec 2022to 3 Aug 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- MDD diagnosis
- Previously tried at least one approved method of treatment for their depression
- No monoamine oxidase-inhibitor class antidepressants for at least 3 months
- Deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, laboratory tests of blood and urine
- No psychedelic drug use in the 6 months before dosing until the end of the study
- Willing to follow the contraception requirements of the trial
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- Willing to be contacted by email and video call, and have online access
- Able to give fully informed written consent
- Test Cohort only: currently on a stable dose of an unspecified single SSRI alone and not in combination with any other psychiatric medications, for at least 6 weeks prior to Screening with no intention of making any changes
- Control Cohort only: no antidepressant medication for 6 months before dosing
Who cannot join
- Substance use disorder
- Current or clinically relevant history of a psychotic disorder, or first-degree relatives with a clinically relevant history of a psychotic disorder
- Significant history of mania
- Significant risk of suicide
- Clinically relevant abnormal findings at the screening assessment
- Blood pressure, heart rate, or QTcF outside the acceptable ranges
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- Acute or chronic illness (other than MDD) or infection
- Clinically relevant abnormal medical history or concurrent medical condition (other than MDD)
- Use of any serotonergic psychedelics within 6 months prior to dosing
- Patients of child-bearing potential who are pregnant or lactating, or who are sexually active and not using a reliable method of contraception
- History of a severe adverse reaction to any drug or sensitivity to serotonergic psychedelic drugs
- Use of over-the-counter or prescribed medication (excluding oral contraceptives, hormone replacement therapy and SSRIs [Test Cohort only]) within previous 28 day before dose of trial medication; or paracetamol or ibuprofen within 4 hours prior to dosing
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
MAC Clinical Research
Liverpool, Prescot, L34 1BH
Mac Clinical Research
Manchester, Greater Manchester, M13 9NQ
About this study
Official title: An Open-Label Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics & Exploratory Efficacy of Intravenous SPL026 Drug Product (DMT Fumarate) Alone or in Combination With SSRIs in Patients With Major Depressive Disorder
The main aim of the study is to test the safety and tolerability of single doses of SPL026 (N,N-dimethyltryptamine [DMT] fumarate, a psychedelic tryptamine) in patients currently taking a selective serotonin reuptake inhibitor (SSRI) for their depression, but for whom the SSRI is not fully relieving their depression.
- Conditions
- Major Depressive Disorder
- Being tested
- SPL026
- Keywords
- Major Depressive Disorder, MDD, Depression, SSRI, N,N-dimethyltryptamine, DMT
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SPL026Drug
Also called N,N-dimethyltryptamine, DMT
Intravenous
| Study group | Role | What they receive |
|---|---|---|
| Test Cohort | Experimental | Patients who are currently taking an SSRI that is not effective in fully relieving their depression (prescribed outside of study). Patients will be administered a single dose of SPL026 by intravenous infusion. Receives: Drug: SPL026 |
| Control Cohort | Experimental | Patients who are not currently taking any pharmacological treatment for their depression. Patients will be administered a single dose of SPL026 by intravenous infusion. Receives: Drug: SPL026 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety & tolerability: Adverse Events
Adverse events (AEs)
Measured: Screening to End-of-Study Follow-up (Day 29)
Safety & tolerability: Lab biochemistry
Values of potential clinical importance
Measured: Screening, Day -1 and Day 1
Safety & tolerability: Vital signs - Heart Rate
Heart rate
Measured: Screening to Day 2
Safety & tolerability: Vital signs - Blood pressure
Blood pressure
Measured: Screening to Day 2
Safety & tolerability: Vital signs - Temperature
Temperature
Measured: Screening to Day 2
Safety & tolerability: Electrocardiogram
QTcX intervals
Measured: Screening to Day 2
Safety & tolerability: Suicidal Ideation
Columbia-Suicide Severity Rating Scale
Measured: Screening to End-of-Study Follow-up (Day 29)
Secondary outcomes (5)
Evaluation of plasma levels of DMT
Pharmacokinetic parameter calculation in the Test Cohort compared to the Control Cohort
Measured: 2, 5, 7, 10, 11, 13, 15, 30, 60, 120, 240 minutes post-dose
Mystical Experience Questionnaire (MEQ)
MEQ in the Test Cohort compared to the Control Cohort
Measured: Day 1 (dosing day)
Challenging Experience Questionnaire (CEQ)
CEQ in the Test Cohort compared to the Control Cohort
Measured: Day 1 (dosing day)
Ruminative Responses Scale (RRS)
RRS in the Test Cohort compared to the Control Cohort
Measured: Day -1 and Day 29
Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS)
WEMWBS in the Test Cohort compared to the Control Cohort
Measured: Day -1, Day 15 and Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2022
- Study start13 Dec 2022
- Primary completion3 Aug 2023
- Study completion3 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Test Cohort of patients already taking an SSRI for their depression, compared to the Control Cohort who are not already taking an SSRI. All patients will receive SPL026
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Small Pharma Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Fabian Devlin, MD, Principal investigator, MAC Clinical ResearchNeel Bhatt, MD, Principal investigator, MAC Clinical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05553691
- Sponsor's protocol ID
- CT026_004
- Other IDs
- 2022-001767-27
- Status last verified
- Jun 2024
- First submitted
- 13 Sep 2022
- Last updated
- 14 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hagel JM, Chang L, Li J, Chen X, Yu L, Gallant JA, Facchini PJ. Bioproduction of a Large-Scale Library of Tryptamine Derivatives for Neuropsychiatric Drug Screening. ACS Chem Biol. 2025 Jun 20;20(6):1212-1231. doi: 10.1021/acschembio.4c00857. Epub 2025 May 15.
PubMed 40375477
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics & Exploratory Efficacy of Intravenous SPL026 Drug Product (DMT Fumarate) Alone or in Combination With SSRIs in Patients With Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT05553691
- Acronym / sponsor ID
- CT026_004
- Conditions
- Major Depressive Disorder
- Keywords
- Major Depressive Disorder, MDD, Depression, SSRI, N,N-dimethyltryptamine, DMT
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Small Pharma LtdIndustry (pharma, biotech, devices)
- Study start
- 13 Dec 2022 (actual)
- Primary completion
- 3 Aug 2023 (actual)
- Study completion
- 3 Aug 2023 (actual)
- First posted
- 23 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main aim of the study is to test the safety and tolerability of single doses of SPL026 (N,N-dimethyltryptamine [DMT] fumarate, a psychedelic tryptamine) in patients currently taking a selective serotonin reuptake inhibitor (SSRI) for their depression, but for whom the SSRI is not fully relieving their depression.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Test Cohort of patients already taking an SSRI for their depression, compared to the Control Cohort who are not already taking an SSRI. All patients will receive SPL026
| Arm | Type | Receives |
|---|---|---|
| Test Cohort | Experimental | Drug: SPL026Patients who are currently taking an SSRI that is not effective in fully relieving their depression (prescribed outside of study). Patients will be administered a single dose of SPL026 by intravenous infusion. |
| Control Cohort | Experimental | Drug: SPL026Patients who are not currently taking any pharmacological treatment for their depression. Patients will be administered a single dose of SPL026 by intravenous infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- MDD diagnosis
- Previously tried at least one approved method of treatment for their depression
- No monoamine oxidase-inhibitor class antidepressants for at least 3 months
- Deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, laboratory tests of blood and urine
- No psychedelic drug use in the 6 months before dosing until the end of the study
Key exclusion criteria (12 listed)
- Substance use disorder
- Current or clinically relevant history of a psychotic disorder, or first-degree relatives with a clinically relevant history of a psychotic disorder
- Significant history of mania
- Significant risk of suicide
- Clinically relevant abnormal findings at the screening assessment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SPL026Also: N,N-dimethyltryptamine, DMTIntravenous | Drug | Control Cohort, Test Cohort |
Primary outcome
Safety & tolerability: Adverse Events
Time frame: Screening to End-of-Study Follow-up (Day 29)
Adverse events (AEs)
Safety & tolerability: Lab biochemistry
Time frame: Screening, Day -1 and Day 1
Values of potential clinical importance
Safety & tolerability: Vital signs - Heart Rate
Time frame: Screening to Day 2
Heart rate
Safety & tolerability: Vital signs - Blood pressure
Time frame: Screening to Day 2
Blood pressure
Safety & tolerability: Vital signs - Temperature
Time frame: Screening to Day 2
Temperature
Safety & tolerability: Electrocardiogram
Time frame: Screening to Day 2
QTcX intervals
Safety & tolerability: Suicidal Ideation
Time frame: Screening to End-of-Study Follow-up (Day 29)
Columbia-Suicide Severity Rating Scale
5 secondary outcomes
Evaluation of plasma levels of DMT
Time frame: 2, 5, 7, 10, 11, 13, 15, 30, 60, 120, 240 minutes post-dose
Mystical Experience Questionnaire (MEQ)
Time frame: Day 1 (dosing day)
Challenging Experience Questionnaire (CEQ)
Time frame: Day 1 (dosing day)
Ruminative Responses Scale (RRS)
Time frame: Day -1 and Day 29
Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS)
Time frame: Day -1, Day 15 and Day 29
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2024.
- Derived from this study: PubMed 40375477Hagel JM, Chang L, Li J, Chen X, Yu L, Gallant JA, Facchini PJ. Bioproduction of a Large-Scale Library of Tryptamine Derivatives for Neuropsychiatric Drug Screening. ACS Chem Biol. 2025 Jun 20;20(6):1212-1231. doi: 10.1021/acschembio.4c00857. Epub 2025 May 15.
- Redacted Clinical Study Report SynopsisLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fabian Devlin, MD principal investigator
MAC Clinical Research
Neel Bhatt, MD principal investigator
MAC Clinical Research
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SPL026 in people with Major Depressive Disorder, run by Small Pharma Ltd at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety & tolerability: Adverse Events (time frame: Screening to End-of-Study Follow-up (Day 29)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05553691, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2024.