Drug SafetyPhase 1THCNCT01740960
Safety and Tolerability of Namisol in the Elderly
A Phase 1 study testing delta-9-tetrahydrocannabinol in people with Drug Safety, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
The results of phase I Namisol® study (Klumpers et al. Br J Clin Pharmacol, 2012), implicate that Namisol® may have a favorable PK and PD characteristics and is safe to use in people. However, the study included only young adults with a mean age of 21.4 years. Read more about this study
- Who is it for?
- Ages 65 years and olderHealthy volunteers can take part
- Conditions the study is for
- Drug Safety
- What is being tested?
- delta-9-tetrahydrocannabinol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- Aug 2012to Dec 2012
- 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 65 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Subject is a healthy old person as established by medical history, physical examination, electrocardiography, results of hematological and biochemical blood tests on screening.
- Age 65 years
- Body mass index between 18.0 and 30 kg m-2
- Subject is able and willing to sign the Informed Consent Form prior to screening evaluations
Who cannot join
- Regular cannabis user, defined as: smoking one or more joints per week
- Documented history of sensitivity/idiosyncrasy to cannabis
- Relevant history or presence of severe pulmonary disorders [e.g. COPD GOLD III or IV], serious cardiovascular disorders [e.g. myocardial infarction < 6 months ago; atrial fibrillation; heart failure NYHA III or IV; severe heart valve disease, orthostatic hypotension defined as systolic drop of 20 mm Hg Safety and Tolerability of Namisol in the Elderly Page 8 Version 2, 10 07 2012 or diastolic drop of 10 mm Hg], seizures, migraine, psychiatric disorders [e.g. depression (based on documented history or GDS-30 on screening ≥ 10); mania; psychosis; dementia], cognitive impairment [based on documented history or MMSE on screening < 28, significant renal (GFR < 30 ml/min) or hepatic disorders [e.g. cancer, cirrhosis. ALT or AST ≥ twice the upper limit of normal], diabetes mellitus, coagulation disorders
- Inability to understand the nature and extent of the trial and the procedures required
- Current alcohol abuse or use of more than 2 alcoholic consumptions daily
- History of, or current drug abuse
Show all 13Show fewer
- Using drugs that are inhibitors of CYP2C9, CYP2C19 and CYP3A4 (see appendix 13.3)
- Participation in a drug trial within 60 days prior to the first intervention day
- Donation of blood within 60 days prior to the first intervention day
- Known lactose intolerance
- Using more than six units of (methyl)xanthine products per day (e.g. coffee, tea, cola, chocolate)
- Smoking more than ten cigarettes per day
- High fall-risk (based on body sway test)
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Medical Centre, department of Geriatrics
Nijmegen, Gelderland
About this study
Official title: Safety and Tolerability of Oral Namisol®, a Tablet Containing Delta-9-Tetrahydrocannabinol, in Elderly Subjects: A Randomized Controlled Trial
The results of phase I Namisol® study (Klumpers et al. Br J Clin Pharmacol, 2012), implicate that Namisol® may have a favorable PK and PD characteristics and is safe to use in people. However, the study included only young adults with a mean age of 21.4 years. In a previous THC study, subjects age has been associated with treatment response and tolerance of adverse reactions. This association was not supported by Lane et al. and Volicer et al.
There is concern about the safety and tolerability of THC in the elderly population. This is because, elderly persons in general have higher risk of adverse drug reactions due to a combination of physiological factors such as decreasing in lean body mass, the reduction of renal and hepatic clearance, and medical comorbidity which can lead to polypharmacy and drug-drug interactions. Therefore, data from the phase I trial cannot be translated directly to an elderly (and likely more vulnerable) population. This makes it important to evaluate the safety and tolerability profiles of different Namisol® doses in the elderly. In our study in progress "Delta-THC in Behavioral Disturbances in Dementia", the Namisol® doses of 0,75 mg and 1,5 mg are, until now, well tolerated by elderly subjects. These doses are, however, very low in comparison with the doses used in phase I study with young adults (5 mg, 6,5 mg and 8 mg). The current study on the safety and tolerability of relatively high doses of Namisol® will help us in the future to provide broad advice on the therapeutic index and safety profile of Namisol® in the elderly population.
Read the detailed description
Subjects will visit the site 5 times. The first visit, is a 2 hour screening visit for eligibility in which volunteers after signing informed consent will have a medical history, physical examination, ECG, hematological and biochemical blood tests, Mini Mental State Examination (MMSE), Geriatric Depression scale (GDS-30) and body sway test.
Eligible subjects will be randomly allocated to receive three doses Namisol® (3 mg or 5 mg or 6,5 mg) and placebo in double-blind crossover design (visit 1 to 4). The wash-out period between visits will be at least 2 weeks to a maximum of 4 weeks. Each visit will be preceded by baseline assessment measures. The safety and tolerability profiles of Namisol® will be evaluated on each intervention visit by using a standardized THC adverse effects checklist and self-reporting, vital signs, 12-lead ECG, body sway, Visual Analogue Scales (subtest feeling high), and Test for Attentional Performance (TAP, subtest alertness) and a follow up phone call the following day. Four blood samples will be collected on each visit to determine the relationship between the pharmacodynamic effects (VAS-feeling high, TAP-alertness and body sway) and the plasma concentrations of THC and its active metabolites 11-OH-THC and THC-COOH. In addition, a blood sample will be only collected on the first intervention day for genotyping of cytochrome P450 enzymes CYP2C9 CYP2C19 and CYP3A4.
- Conditions
- Drug Safety
- Being tested
- delta-9-tetrahydrocannabinol, Placebo
- Keywords
- delta-9-tetrahydrocannabinol, THC, Cannabis
- Medical subject headings
- Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
delta-9-tetrahydrocannabinolDrug
Also called Namisol, Cannabis, ECP002A
During the intervention phases, subjects will be randomly allocated to receive 1 of 3 doses Namisol®: 3 mg, 5 mg, 6,5 mg (or placebo) The washout period between the intervention periods will be at least 2 weeks.
PlaceboDrug
Also called The control product is placebo
On each intervention day the subjects will receive the same amount of drugs in order to insure the blinding of the study
| Study group | Role | What they receive |
|---|---|---|
| delta-9-tetrahydrocannabinol | Active comparator | Subjects will be randomized to receive 3 doses Namisol® (3 mg, 5 mg, 6,5 mg) Receives: Drug: delta-9-tetrahydrocannabinol |
| Placebo | Placebo comparator | The control product is placebo, consisting of a tablet with similar appearance and taste of the test product. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
THC adverse effects checklist and self-reporting by the subjects
Safety and tolerability of Namisol® will be evaluated by assessing the incidence and severity of adverse events on each intervention visit by using a standardized THC adverse effects checklist and self-reporting by the subjects.
Measured: Pre dose, 0h30m, 1h30m and at 2h30m post ingestion
Secondary outcomes (4)
Body Sway Test (SwayStar™)
On each intervention visit the body sway will be assessed by using the SwayStar®.The SwayStar® device consists of 2 digitally-based angular velocity transducers and is worn on the lower back (at the level of the lumbar spine, lumbar 2-3). It is a wireless device, which makes it possible to examine subjects" balance while walking. The transducers can accurately assess angular movement and angular velocities in 2 directions: anterior-posterior (pitch plane) and mediolateral (roll plane)
Measured: Pre dose, 0h40m, 0h55m and at 2 hour post ingestion
Visual analogue scales, subtest "feeling high"
The Bowdle visual analogue scales (VAS) of psychedelic effects will be performed on each intervention visit in order to measure subjective feeling high
Measured: Pre dose, 0h40m, 0h55m and at 2 hour post ingestion
Test for Attentional Performance (TAP), subtest alertness
On each intervention visit the alertness of subjects will be measured by using the TAP. The TAP subtest "Alertness" measures the subject's ability to respond to a visual stimulus and to increase the attentional level in expectance of a stimulus of high priority. The computer-assisted test is given under 2 conditions: (1) Simple reaction time to a visual stimulus (Greek cross) appearing at randomly varying intervals on the monitor screen is measured. (2) In the second condition, the visual stimulus (= critical stimulus) is preceded by a cue sound presented as warning tone.
Measured: Pre dose, 0h40m, 0h55m and at 2 hour post ingestion
Plasma concentrations of THC and its active metabolites 11-OH-THC and THC-COOH
Four blood samples will be collected on each visit to determine the relationship between the pharmacodynamic effects ( using VAS-feeling high, TAP-alertness and body sway) and the plasma concentrations of THC and its active metabolite 11-OH-THC and THC-COOH.
Measured: Pre dose, 0h40m, 0h55m and at 2 hour post ingestion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2012 (estimated)
- Study startAug 2012
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug SafetyStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marcel Olde Rikkert, prof. dr., Principal investigator, Radboud University Medical Center Nijmegen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01740960
- Sponsor's protocol ID
- GER001-02-03
- Other IDs
- 2012-001841-42
- Acronym
- THC
- Status last verified
- Jul 2012
- First submitted
- 15 Nov 2012
- Last updated
- 7 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Tolerability of Oral Namisol®, a Tablet Containing Delta-9-Tetrahydrocannabinol, in Elderly Subjects: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01740960
- Acronym / sponsor ID
- THC / GER001-02-03
- Conditions
- Drug Safety
- Keywords
- delta-9-tetrahydrocannabinol, THC, Cannabis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Aug 2012
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 4 Dec 2012 (estimated)
- 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 results of phase I Namisol® study (Klumpers et al. Br J Clin Pharmacol, 2012), implicate that Namisol® may have a favorable PK and PD characteristics and is safe to use in people. However, the study included only young adults with a mean age of 21.4 years. In a previous THC study, subjects age has been associated with treatment response and tolerance of adverse reactions. This association was not supported by Lane et al. and Volicer et al.
There is concern about the safety and tolerability of THC in the elderly population. This is because, elderly persons in general have higher risk of adverse drug reactions due to a combination of physiological factors such as decreasing in lean body mass, the reduction of renal and hepatic clearance, and medical comorbidity which can lead to polypharmacy and drug-drug interactions. Therefore, data from the phase I trial cannot be translated directly to an elderly (and likely more vulnerable) population. This makes it important to evaluate the safety and tolerability profiles of different Namisol® doses in the elderly. In our study in progress "Delta-THC in Behavioral Disturbances in Dementia", the Namisol® doses of 0,75 mg and 1,5 mg are, until now, well tolerated by elderly subjects. These doses are, however, very low in comparison with the doses used in phase I study with young adults (5 mg, 6,5 mg and 8 mg). The current study on the safety and tolerability of relatively high doses of Namisol® will help us in the future to provide broad advice on the therapeutic index and safety profile of Namisol® in the elderly population.
Detailed description
Subjects will visit the site 5 times. The first visit, is a 2 hour screening visit for eligibility in which volunteers after signing informed consent will have a medical history, physical examination, ECG, hematological and biochemical blood tests, Mini Mental State Examination (MMSE), Geriatric Depression scale (GDS-30) and body sway test.
Eligible subjects will be randomly allocated to receive three doses Namisol® (3 mg or 5 mg or 6,5 mg) and placebo in double-blind crossover design (visit 1 to 4). The wash-out period between visits will be at least 2 weeks to a maximum of 4 weeks. Each visit will be preceded by baseline assessment measures. The safety and tolerability profiles of Namisol® will be evaluated on each intervention visit by using a standardized THC adverse effects checklist and self-reporting, vital signs, 12-lead ECG, body sway, Visual Analogue Scales (subtest feeling high), and Test for Attentional Performance (TAP, subtest alertness) and a follow up phone call the following day. Four blood samples will be collected on each visit to determine the relationship between the pharmacodynamic effects (VAS-feeling high, TAP-alertness and body sway) and the plasma concentrations of THC and its active metabolites 11-OH-THC and THC-COOH. In addition, a blood sample will be only collected on the first intervention day for genotyping of cytochrome P450 enzymes CYP2C9 CYP2C19 and CYP3A4.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| delta-9-tetrahydrocannabinol | Active comparator | Drug: delta-9-tetrahydrocannabinolSubjects will be randomized to receive 3 doses Namisol® (3 mg, 5 mg, 6,5 mg) |
| Placebo | Placebo comparator | Drug: PlaceboThe control product is placebo, consisting of a tablet with similar appearance and taste of the test product. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- Subject is a healthy old person as established by medical history, physical examination, electrocardiography, results of hematological and biochemical blood tests on screening.
- Age 65 years
- Body mass index between 18.0 and 30 kg m-2
- Subject is able and willing to sign the Informed Consent Form prior to screening evaluations
Key exclusion criteria (13 listed)
- Regular cannabis user, defined as: smoking one or more joints per week
- Documented history of sensitivity/idiosyncrasy to cannabis
- Relevant history or presence of severe pulmonary disorders [e.g. COPD GOLD III or IV], serious cardiovascular disorders [e.g. myocardial infarction < 6 months ago; atrial fibrillation; heart failure NYHA III or IV; severe heart valve disease, orthostatic hypotension defined as systolic drop of 20 mm Hg Safety and Tolerability of Namisol in the Elderly Page 8 Version 2, 10 07 2012 or diastolic drop of 10 mm Hg], seizures, migraine, psychiatric disorders [e.g. depression (based on documented history or GDS-30 on screening ≥ 10); mania; psychosis; dementia], cognitive impairment [based on documented history or MMSE on screening < 28, significant renal (GFR < 30 ml/min) or hepatic disorders [e.g. cancer, cirrhosis. ALT or AST ≥ twice the upper limit of normal], diabetes mellitus, coagulation disorders
- Inability to understand the nature and extent of the trial and the procedures required
- Current alcohol abuse or use of more than 2 alcoholic consumptions daily
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 |
|---|---|---|
| delta-9-tetrahydrocannabinolAlso: Namisol, Cannabis, ECP002ADuring the intervention phases, subjects will be randomly allocated to receive 1 of 3 doses Namisol®: 3 mg, 5 mg, 6,5 mg (or placebo) The washout period between the intervention periods will be at least 2 weeks. | Drug | delta-9-tetrahydrocannabinol |
| PlaceboAlso: The control product is placeboOn each intervention day the subjects will receive the same amount of drugs in order to insure the blinding of the study | Drug | Placebo |
Primary outcome
THC adverse effects checklist and self-reporting by the subjects
Time frame: Pre dose, 0h30m, 1h30m and at 2h30m post ingestion
Safety and tolerability of Namisol® will be evaluated by assessing the incidence and severity of adverse events on each intervention visit by using a standardized THC adverse effects checklist and self-reporting by the subjects.
4 secondary outcomes
Body Sway Test (SwayStar™)
Time frame: Pre dose, 0h40m, 0h55m and at 2 hour post ingestion
Visual analogue scales, subtest "feeling high"
Time frame: Pre dose, 0h40m, 0h55m and at 2 hour post ingestion
Test for Attentional Performance (TAP), subtest alertness
Time frame: Pre dose, 0h40m, 0h55m and at 2 hour post ingestion
Plasma concentrations of THC and its active metabolites 11-OH-THC and THC-COOH
Time frame: Pre dose, 0h40m, 0h55m and at 2 hour post ingestion
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 7 Jan 2014.
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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.
Marcel Olde Rikkert, prof. dr. principal investigator
Radboud University Medical Center Nijmegen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing delta-9-tetrahydrocannabinol in people with Drug Safety, run by Radboud University Medical Center at 1 site in Netherlands.
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 4 inclusion and 13 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 7 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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. Some participants in this study may receive a placebo. 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?
THC adverse effects checklist and self-reporting by the subjects (time frame: Pre dose, 0h30m, 1h30m and at 2h30m post ingestion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Jan 2014.