Primary ObjectiveTo assess the treatment efficacy vs placebo of repeated low doses (20 µg) of LSD for six weeks in adult patients with ADHD measured by Adult Attention Deficit Investigator Symptom Rating Scale (AISRS).Secondary Objectives1. To…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Attention Deficit Hyperactivity Disorder
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
Mean change from baseline in ADHD symptoms, as assessed by the AISRS after 6
weeks of treatment. The AISRS total score consists of 18 items from the
original Attention- Deficit/Hyperactivity Disorder - Rating Scale (ADHD-RS),
which were derived based on DSM-5 criteria for ADHD. The
ADHD-RS includes 9 items that address symptoms of inattention, and 9 items that
address symptoms of impulsivity and hyperactivity. Each item is rated from 0 to
3. The AISRS total score can range from 0 to 54. A higher score corresponds to
a worse severity of ADHD.
Secondary outcome
Secondary endpoints:
ADHD-related endpoints:
* key secondary endpoint: change from baseline in AISRS after 1 week (2 doses)
of treatment.
* occurrence of patients who experience at least a 1-point decrease in the CGI-S
* change from baseline in CGI-S after 1 week (2 doses) of treatment and after 6
weeks of treatment
* change from baseline in patient self-assessment by the Adult ADHD Self-Report
Scale (ASRS) and Connors* Adult ADHD Rating Scale (CAARS).
Safety Endpoints
* vital signs (supine blood pressure, heart rate)
* 12-lead safety ECG
* psychological and/or physiological adverse events
* Safety laboratory evaluation and Urine pregnancy testing
* Columbia-Suicide Severity Rating Scale (C-SSRS)
Background summary
There is a growing interest in the use of psychedelic substances for
health-related purposes, including symptom relief for disorders like anxiety,
depression, and pain (Nichols et al., 2017). Although the focus of recent
clinical trials have used high doses of these substances, anecdotal evidence
supports the potential therapeutic utility of lower doses of psychedelic
substances in reducing symptomatology of a range of mental and physiological
disorders (Anderson et al., 2019a; Anderson et al., 2019b; Fadiman et al.,
2019; Hutten et al., 2019a; Hutten et al., 2019b; Lea et al., 2020; Passie,
2019; Polito et al., 2019; Prochazkova et al., 2018). The internet has a number
of surveys, chat rooms and coaches touting the benefits of psychedelics,
particularly LSD at sub-perceptual doses to treat ADHD, anxiety, and
depression. It has yet to be shown whether a psychedelic experience as induced
by a *full* regular dose is necessary to produce symptom relief, or whether
(repeated) sub-perceptual doses have therapeutic potential as well.
Recently microdosing, the practice of repeatedly using low doses of
psychedelics like lysergic acid diethylamide (LSD) and psilocybin (Kuypers et
al., 2019; Passie, 2019), has gained considerable media attention, where it is
portrayed as a performance enhancing activity (Hutten et al., 2019b), and as a
treatment for certain diseases like depression, anxiety and ADHD. In contrast
to a regular dose (approximately 100 mcg) that is characterized by perceptual
changes, a microdose (approximately 10 to 20 mcg) does not induce relevant
perceptual alternations (Bershad et al., 2019; Family et al., 2020; Kuypers et
al., 2019; Passie, 2019). The most widely suggested practice is taking
one-tenth of a regular, recreational dose of a psychedelic once every three
days (Fadiman et al., 2019; Kuypers et al., 2019; Passie, 2019).
Clinical study evidence regarding the efficacy of microdosing with psychedelics
for symptomatic relief is lacking. However, recent surveys have provided data
on potential benefits of microdosing LSD. Specifically, microdosing
psychedelics was rated more effective than conventional therapies for the
treatment of ADHD by persons using psychedelics (Hutten et al., 2019b). Users
mostly report microdosing psychedelics for performance enhancement (Hutten et
al., 2019a; Lea et al., 2019; Lea et al., 2020) and to improve mental health
(Lea et al., 2019; Lea et al., 2020). Other reasons are mood enhancement and
symptom relief, curiosity, and enhancing empathy (Hutten et al., 2019a). Taken
together, that survey data indicate that people microdose as self-medication
therapy for mental health as alternative or adjunct to conventional therapy
(Lea et al., 2020). Adverse effects of microdosing include
stronger-than-expected psychedelic effects, anxiety, and physical adverse
effects (Lea et al., 2020). Other perceived limitations include issues related
to dosing, taking illegal substances, limited or no mental health or cognitive
improvement, unpleasant *off* days, only short-term benefits, and concerns
about dependence and drug-related risks (Lea et al., 2019). Large other
non-published survey data also indicates that people microdose to enhance mood,
creativity, focus, and sociability. Concerns about adverse health effects are
rather small. However, there is no controlled data on either the efficacy or
adverse effects of microdosing psychedelics, including LSD. Therefore, the
present study aims to investigate the effectiveness of microdosing with LSD for
treatment of ADHD in line with a common but not-controlled practice. The
present study will include an assessment of the pharmacokinetics and acute
effects of 20 mcg of LSD over 6 hours during first dosing at the hospital. The
same dose will then be administered twice weekly and effects compared with
placebo in a double-blind manner over 6 weeks regarding benefits in adult
patients with ADHD.
Study objective
Primary Objective
To assess the treatment efficacy vs placebo of repeated low doses (20 µg) of
LSD for six weeks in adult patients with ADHD measured by Adult Attention
Deficit Investigator Symptom Rating Scale (AISRS).
Secondary Objectives
1. To assess treatment efficacy vs placebo measured by change from baseline in
AISRS after 1 week of treatment.
2. To assess treatment efficacy vs placebo based on the proportion of patients
who experience at least a 1-point decrease in the Clinical Global Impression -
Severity of Illness Scale (CGI-S).
3. To assess treatment efficacy vs placebo measured by change from baseline in
CGI-S.
4. To assess the safety and tolerability by Adverse Event (AE) and Serious
Adverse Event (SAE) assessment.
Study design
This study is a multi-center, randomized, double-blind, placebo-controlled
Phase 2a study of low dose MM-120 (20 µg) compared with a placebo administered
for 6 weeks (twice a week on a 3/4-day schedule [± 1 day]).
Intervention
There will be 2 arms:
* Arm 1-Placebo: a total of 26 patients will receive a placebo identical in
appearance to the investigational medicinal product (IMP) administered orally
twice weekly (e.g., Tuesday/Friday) for 6 weeks.
* Arm 2-MM-120: a total of 26 patients will receive 20 µg of M-120 administered
orally twice weekly for 6 weeks.
Study burden and risks
The total time investment for the participant is estimated at approximately 26
hours.
This is divided over a maximum of 15 visits over a period of 14 weeks.
This includes the time a participant spends keeping a daily diary.
During participation in the study, a blood sample is taken 13 times (7 times
7,5 ml via an inserted intravenous catheter and 6 times 10 ml via venipuncture).
At each visit the participant is asked to fill in a number of questionnaires.
Prior to participation a screening visit takes place to see if the participant
is physically and mentally eligible to participate.
During this visit it is also checked whether the criterion of having sufficient
ADHD complaints is met.
If a participant qualifies for participation and uses ADHD medication, he or
she will be asked to discontinue this from the medical screening until the end
of participation in the study.
For all visits, on which the participant is given a dose of LSD, they are asked
to come to the clinic with a caregiver, or be prepared to take a taxi home and
not drive a car or use heavy equipment or other dangerous activities if they
are under the influence for the rest of the evening, until the next morning.
The use of LSD can have side effects.
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Age
Inclusion criteria
1. Ability and willingness to provide written, informed consent prior to
initiation of any
study-related procedures and to adhere to all study requirements.
NOTE: The subject (i.e., not a legally authorized representative) must be
cognitively
able to understand the requirements of the study and provide the informed
consent.
2. Age >= 18 and <= 65 years at screening.
3. Subjects with the diagnosis of Diagnostic and Statistical Manual of Mental
Disorders-
5 (DSM-5) ADHD, as determined by clinical evaluation and confirmed by structured
interview (MINI).
4. AISRS total score of >=26 at screening.
5. CGI-S score of >=4 at screening.
6. Must be willing to receive IMP dose twice weekly. On Day 1, the subject will
come to
the clinic and must be willing to take a taxi or public transportation home or
be
accompanied by a caregiver and not drive a car, use heavy equipment, or
participate in
any other dangerous activity for the remainder of the day after receiving IMP
(NOTE:
at any protocol visit after Day 1 dosing, dosing visits may occur at the
subject*s home
at the discretion of the PI, conducted by one of the study investigators or
delegate and
administered under supervision followed by the performance of the same
procedures
done at the clinic including safety monitoring. If early withdrawal is
considered due to
any safety issue identified, the Sponsor*s medical monitor should be notified.
If a
remote visit is conducted due to any reason related to the COVID-19 pandemic,
notification must be sent to the Medical Monitor*s dedicated email address and
Urgent
Safety Measures as outlined in this protocol must be followed.)
7. Must be willing to refrain from more than 6 standard alcoholic drinks per
week
(1 standard drink corresponds to 0.1 L wine, 0.3 L beer, or 4 cL liquor), more
than 10
cigarettes a day, and more than 2 cups of coffee a day throughout the study
treatment
period (6 weeks) and until the last study visit is complete (EoS or ET).
Exclusion criteria
1. Past or present diagnosis of a primary psychotic disorder or first-degree
relative with a
psychotic disorder.
2. Past or present bipolar disorder (DSM-5).
3. Other current psychiatric disorders that, in the opinion of the Investigator
or medical
supervisor, may confound the results of the study (e.g., obsessive-compulsive
disorder,
dysthymic disorder, panic disorder, dissociative disorder, anorexia nervosa or
bulimia
nervosa).
4. Subjects with past (> 1 month prior to the screening visit) or present
substance use
disorder (except nicotine, provided subject does not smoke more than 10
cigarettes a
day).
5. Somatic disorders including Central Nervous System (CNS) involvement of
cancer,
severe cardiovascular disease, untreated hypertension, severe liver disease
(liver
enzyme increase by more than 3x the upper limit of normal except unconjugated
hyperbilirubinemia due to Gilbert*s Disease, per Investigator), severely
impaired renal
function (estimated creatinine clearance < 50 mL/min by CKD-EPI formula), or
anything else that, in the judgment of the Investigator or medical supervisor,
poses too
great a potential for side effects.
6. Any lifetime history of suicide attempt; or recent (within 6 months prior to
the screening
visit) active suicidal thoughts or ideation (defined as a suicidal ideation
score of 2 or
greater in the Columbia-Suicide Severity Rating Scale [C-SSRS]); or endorsement
of
any suicidal behavior on the C-SSRS within the past 6 months prior to the
screening
visit.
7. Likely to require psychiatric hospitalization during the course of the study.
8. Once consent is signed, subject not willing or able to stop any prescription
or nonprescription
ADHD medications during screening and prior to the baseline visit through
final study visit (EoS or ET). A list of prohibited medications is provided in
Appendix 1.
9. Plan to start, stop, or alter the use of any medications, supplements, or
other therapeutics
from Baseline until EoS or ET (see Appendix 1 for list of prohibited
medications).
10. Plan to start, stop or alter the use of psychotherapy, massage, meditation,
acupuncture,
hypnosis, yoga, or other similar therapy/activity from the time of providing
informed
consent until EoS or ET.
11. Use of potent CYP2D6 inhibitors; moderate CYP2D6 inhibitors by Investigator
discretion (see Section 5.5.1.1 and Appendix 3).
12. Likely to need use of any psychiatric medications with the potential to
confound
interpretation of study results or impact safety, at the discretion of the
Investigator, in
the 10 weeks following Baseline up to EoS or ET (see Appendix 1 for list of
prohibited
medications).
13. Use of investigational medication/treatment in the past 30 days prior to
the screening
visit.
14. Subjects with a positive urine drug screen (with the exception of THC or
metabolites)
at Screening OR Baseline.
15. Clinically significant abnormal baseline laboratory values, VSs, and ECG
that include
the following:
a. Have evidence of clinically significant hepatic disorder (e.g., alanine
aminotransferase [ALT] or aspartate aminotransferase [AST] > 3X ULN
(except for Gilbert*s disease), and
b. Any clinically significant abnormal metabolic or hematologic screen, per
Investigator or medical supervisor decision
c. Exclusionary blood pressure: >140 mm Hg (systolic) or >90 mm Hg (diastolic);
heart rate <45 beats/minute or >90 beats/minute after an approximately 5-
minute supine or semi-supine rest
NOTE: If the first measurement of a subject*s heart rate is > 90 beats/minute, a
second recording is allowed after an additional approximately 5-minute supine
rest
d. Exclusionary ECG parameters: QTcF > 450 msec (men), QTcF >470 msec
(women)
e. Any clinically significant abnormal electrocardiogram (ECG) finding (e.g.,
uncontrolled atrial fibrillation, ischemia) at Screening (Visit 1) or Baseline
(Visit 2), as determined by the Investigator or medical supervisor (in
consultation with a cardiologist, if needed.
16. Any other condition, therapy, laboratory abnormality, or other circumstance
that, in the
opinion of the Investigator or medical supervisor, may pose additional risk to
the subject
from participation in the study, may interfere with the subject*s ability to
comply with
study procedures, may make participation in the study not in the subject*s best
interest
or may confound the results of the study.
17. Prior history or ongoing neuropsychiatric signs or symptoms associated with
COVID-
19 such as development of, or current disorder, during or after a COVID-19
infection
including anxiety, memory loss, confusion, depression, delirium, agitation, or
psychosis.
18. Women of childbearing potential (WOCBP) (i.e., physiologically capable of
becoming
pregnant) who are unwilling or unable to use a highly effective method of
contraception, as defined in Appendix 2, for the duration of the study, OR Men
physiologically capable of fathering a child who are sexually active with WOCBP
but
are unwilling or unable to use barrier contraception (e.g., condom with or
without
spermicidal cream or jelly) for the duration of the study.
NOTE: See Appendix 2 for definitions of WOCBP and highly effective methods of
contraception and for information about unacceptable methods of contraception.
19. Women who are currently pregnant or breastfeeding or plan to become
pregnant or
breastfeed during the study.
20. Men who plan to donate sperm during the study.
21. Use of weight loss drugs within 21 days of screening until the end of study.
22. Subjects who are either unable or unwilling to consume alcohol in any amount
(including due to religious or personal reasons).
23. Subjects who have a change in AISRS score of >=13-points between screening
and
baseline visits.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-001098-55-NL |
| ClinicalTrials.gov | NCT05200936 |
| CCMO | NL73910.068.20 |