Adverse Mental/Physical Effects of Low Dose S. Tortuosum.Phase 1NCT01805518
Safety Study of the Effect of Scelectium Tortuosum (as Zembrin®)in Aged Normals
A Phase 1 study testing Scelectium Tortuosum in people with Adverse Mental/Physical Effects of Low Dose S. Tortuosum., run by Woodbury, Michel, M.D. at 1 site in Puerto Rico.
Trial summary
Phosphodiesterase is a candidate for the Rx \& prevention of cognitive and psychotic disorders. Since caffeine targets primarily PDE4(Phosphodiesterase subtype 4), caffeine analogs have been developed to mimic the actions of caffeine's ability to inhibit PDE-a, PDE4, PDE5 and adenosine-2 (AD-2)but are limited by the… Read more about this study
- Who is it for?
- Ages 45 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Adverse Mental/Physical Effects of Low Dose S. Tortuosum.
- What is being tested?
- Scelectium Tortuosum
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 sitePuerto Rico
- Study dates
- Jun 2011to Mar 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 45 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female Age: 45-65 Absence of DSM IV-R diagnosis As established by Mini-Psychiatric Interview HAM-D < 8 Body Mass Index (BMI) < 30.0 Not Suicidal
Who cannot join
- Current (past 2 months) substance use disorder, Abuse of Caffeine Severe nicotine dependence Abuse of herbal and dietary supplements Current or planned pregnancy (for female) A major DSM IV-R psychiatric diagnosis.
- Serious and unstable medical disorders:
- Recent myocardial ischemia or infarction, unstable angina, uncontrolled hypertension, poor glycemic control in Diabetes mellitus, Renal failure and serious renal diseases, Chronic active hepatitis, acute hepatitis, cirrhosis of liver, AIDS Active malignancy Neurological disorders: epilepsy Recent Traumatic brain injury Active suicidal risk Cerebrovascular disorders: recent stroke Inability to read nor write
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 9 wk, Randomized, 2-blind, Placebo-controlled, 2X2 Cross-over Phase 1 Study of 25 mg of Scelectium Tortuosum (as Zembrin®) in Aged Normals to Find Effects on Mental, Emotional and Cognitive Safety Measures and Cytokines.
Phosphodiesterase is a candidate for the Rx \& prevention of cognitive and psychotic disorders. Since caffeine targets primarily PDE4(Phosphodiesterase subtype 4), caffeine analogs have been developed to mimic the actions of caffeine's ability to inhibit PDE-a, PDE4, PDE5 and adenosine-2 (AD-2)but are limited by the side effects of insomnia and heightened anxiety. Sildenafil (PDE-5 inhibitor) fails to enhance cognition in schizophrenia.
The study of PDE-4 in cognition in Alzheimer's dementia and schizophrenia has been done using the PDE-4 prototypal compound, rolipram, which improves cognition in rodents. Rolipram reverses the memory deficits induced by amyloid fragment Abeta25-35 and Abeta1-40 peptide. In humans the frequent side effect of vomiting hampers translational research. The clinical trial of rolipram in multiple sclerosis was terminated prematurely due to serious adverse events with paradoxical increases in MRI MS-specific brain lesions. However, PDE-4 remains paradigm for cognition.
Read more
Another strategy is chemical moieties capable of antagonizing the PDE-4 through allosteric modulation, rather than direct competitive inhibition hoping to minimize adverse events while retaining the biological potencies and functional responses of PDE-4 Modulators. Dietary supplements with PDE-4 effects have advantages in that small investments are needed to adequately study them.
Pharmacologically active chemicals of Sceletium species are mesembrine-type alkaloids that have proven PDE-4 activity. The PDE-4D knockout mice have enhanced memory function mediated through hippocampal neurogenesis via phosphorylated cAMP response element binding protein (pCREB) signaling.
This study purpose is to delineate the relationship of PDE-4 and cognition in normals. pCREB is possibly the putative biomarker of PDE-4 response with CREB as effector signaling pathway of PDE-4. CREB is close to nuclear receptors represented by BDNF (Brain Derived Neurotrophic Factor) and PPAR (Peroxisome Proliferator Activating Receptor) complexes. CREB changes in neuronal plasticity are targets for pharmacological paradigms for cognitive enhancement. This study will use the scelectium tortuosum as manufactured as Zembrin®. The findings in control subjects will form the basis for designing future studies of Zembrin® in neurodegenerative disorders with marked cognitive impairment such as Alzheimer's Dementia and Parkinson's Disease.
Read the detailed description
- Contextual Background For the past decade, converging evidence suggests that targeting PD Phosphodiesterase for cognition represents novel heuristic approaches for development of dietary supplements and drug candidates for the treatment and prevention of cognitive and psychotic disorders.
- . The earlier findings on caffeine as the prototypal PD inhibitor targeting primarily PDE4 (Phosphodiesterase subtype 4) has stimulated synthesis of caffeine analogs to improve upon the pharmacokinetic profile and benefits/risk ratio.
- . The dual actions of caffeine as inhibitor of PDE-a, PDE4 and PDE5 and adenosine-2 (AD-2) antagonist, exerts multiple brain-behavior functions including sleep, cognition, memory and learning. It remains to be seen whether caffeine analogues live up the therapeutic potential in neurodegenerative diseases while bypassing the side effects of insomnia and heightened anxiety. Sildenafil (Viagra R) PDE-5 inhibitor indicated for erectile dysfunction (ED) fails to enhance cognition in schizophrenia
- . The full dosage range may not have been explored in the study with sildenafil. It is noteworthy that PDE-5 inhibition is related to NMDA (N-methyl-d-aspartic acid) glutamatergic modulation. In conducting a Pub Med search of recent studies point to the role of PDE-4 in diverse domains of cognition: memory, attention, executive function, recall, visual-spatial tasks. We find converging evidence targeting PDE-4 as the novel approach towards treating the cognitive deficits in Alzheimer dementia and schizophrenia
- . Most of the preclinical studies focus exclusively on the PDE-4 prototypal compound, rolipram. Rolipram improves memory consolidation, working memory and information processing in rodent species subjected to a variety of cognitive tasks: radial arm maze, passive avoidance, delayed arm water maze
- . A very recent study found that rolipram, reverses deficits induced by amyloid fragment Abeta25-35 and Abeta1-40 peptide in the Morris water maze and passive avoidance task
- . In preclinical screening of PDE-4 inhibitors, vomiting mediated via activating the area postema has been consistently noted. Tolerability and safety has hampered significantly the translation research in PDE-4 inhibitors. The clinical trial of rolipram in multiple sclerosis was terminated prematurely due to serious adverse events with paradoxical increases in MS-specific brain lesions identified by MRI
- . Notwithstanding the challenges in translational research, the molecular template of PDE-4 remains a highly viable paradigm for cognition. Drug Design has adopted another strategy in developing chemical moieties capable of antagonizing the PDE-4 pharmacological effects. Through allosteric modulation, rather than direct competitive inhibition at the catalytic site domain of PDE-4, the hope is to minimize the adverse events while retaining the biological potencies and functional responses relevant to the pharmacological activities of PDE-4 compounds.
- . The emergence of PDE-4 Modulators (PDE-4M) has attracted attention. Dietary supplements possessing the molecular templates and requirements in PDE-4 design strategy have added advantages in that preliminary clinical studies can be undertaken with a disproportionately small investment. If the preliminary results are favorable, strategic advances to GMP patented drug candidates are more predictable and confer less fiscal and clinical risks without compromising the efficacy stipulation in satisfying FDA criteria for phase II and Phase III trials. Our study the Zembrin® formulation of Scelectium Toruosum in cognition expands on an earlier study protocol which investigated the effects of Zembrin® in Generalized Anxiety Disorder (GAD). The pharmacologically active chemicals from the Sceletium species belong to mesembrine-type alkaloids; the structures are well characterized. Structure-activity relationship of the mesembrine-derivative alkaloids has been delineated in in-vitro assay of recombinant PDE-4 regarding the relative potencies in producing the functional responses. The IC50 of mesembrine-HCL is determined to be 20 microM
- . The PDE-4D knockout mice model provides evidence of enhanced memory function is mediated through hippocampal neurogenesis via phosphorylated cAMP response element binding protein (pCREB) signaling.
- . Microinfusion of lentiviral vectors carrying micro RNAs targeting the long-form of PDE4D isoforms directly into bilateral dentate gyrus of the hippocampus in the mice resulted in improved performance scores in object recognition test, water maze and radial arm maze. These considerations lead us to organize a pilot "proof-of-concept study" to delineate the relationship of PDE-4 and cognition in normal control subjects to validate the target of PDE-4 in modulating cognition functions in normal control subjects. It is noteworthy that none of the preliminary studies include measure of cAMP signaling in clinical subjects to correlate with brain-behavior interactions. With the availability of sensitive, reliable and valid ELISA method of assaying for pCREB, we consider it important to examine pCREB as the putative biomarker of PDE-4 response in clinical subjects treated with Zembrin®. There is emerging an increase of evidence in support of the construct that CREB as the effector signaling pathway of PDE-4, is the target of diverse classes of antidepressants
- . CREB is the late molecular partner to the family of nuclear receptors represented by BDNF (Brain derived neurotrophic factor) and PPAR (Peroxisome Proliferator Activating Receptor) complex
- . CREB reflects changes in neuronal plasticity and is sensitive to pharmacological paradigms for cognitive enhancement. CREB signaling integrates signal transduction from related neurotransmitters and neuromodulators besides PDE-4. Neuronal alpha-7 nicotinic receptor agonist A-582941 exerts its cognitive effects through interacting with phosphorylation of CREB pathway (13). The findings in control subjects will form the rational basis for designing controlled studies of Zembrin® in neurodegenerative disorders with marked cognitive impairment such as Alzheimer's Dementia and Parkinson's Disease.
- Being tested
- Scelectium Tortuosum
- Keywords
- CNSVS, Tower of London, Letter-Number Test, Trail Making Test, Vital signs, Mood, Suicidal ideation, ECG, Physical exam, Blood, Urine (Including pregnancy and drug screen), Cytokines, Side effects, Brief Psychiatric Rating Scale, Positive and Negative Symptom Scale
- Medical subject headings
- Suicidal Ideation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Scelectium TortuosumDietary supplement
Also called Zembrin
One arm has subjects 3 weeks on Scelectium Tortuosum 25gm po/d then 3 weeks off and then 3 weeks on Placebo.
The other arm has subjects 3 weeks on placebo, then 3 weeks off and then 3 weeks on Scelectium Tortuosum 25mg po/d.
| Study group | Role | What they receive |
|---|---|---|
| Scelectium Tortuosum | Active comparator | S Tortuosum Receives: Dietary Supplement: Scelectium Tortuosum |
| Sugar pill/placebo | Placebo comparator | Sugar pill/placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
CNS Vital Signs
CNS Vital Signs is a measure of cognitive functioning and is done four times, once before the first arm and repeated after the end of the first arm three weeks later. Then after a 3 week washout the measure is repeated, the 2nd arm started and at the end of 3 weeks, it is repeated again.
Measured: 4 times over 9 weeks
Secondary outcomes (10)
Side effect questionnaire
Side effects will be assessed four times, once before the first arm and repeated after the end of the first arm three weeks later. Then after a 3 week washout the measure is repeated, the 2nd arm started and at the end of 3 weeks, it is repeated again.
Measured: 4 times over 9 weeks
Columbia Suicide Scale
This specific suicide assessment questionnaire is given four times, once before the first arm and repeated after the end of the first arm three weeks later. Then after a 3 week washout the measure is repeated, the 2nd arm started and at the end of 3 weeks, it is repeated again.
Measured: 4 times over 9 weeks
ECG
It is done four times, once before the first arm and repeated after the end of the first arm three weeks later. Then after a 3 week washout the measure is repeated, the 2nd arm started and at the end of 3 weeks, it is repeated again.
Measured: 4 times over 9 weeks
Vital Signs
Height, weight, blood pressure, fat content are measured four times, once before the first arm and repeated after the end of the first arm three weeks later. Then after a 3 week washout the measure is repeated, the 2nd arm started and at the end of 3 weeks, it is repeated again.
Measured: 4 times over 9 weeks
Physical Exam
A complete physical is done four times, once before the first arm and repeated after the end of the first arm three weeks later. Then after a 3 week washout the measure is repeated, the 2nd arm started and at the end of 3 weeks, it is repeated again.
Measured: 4 times over 9 weeks
Urine
Urine is take to be analysed at every visit, and is done four times, once before the first arm and repeated after the end of the first arm three weeks later. Then after a 3 week washout the blood serum is taken again, the 2nd arm started and at the end of 3 weeks, it is repeated again. The urine is sent for analysis, drug screen and if a fertile female a pregnancy test.
Measured: 4 collections over 9 weeks
Brief Psychiatric Scale and Positive and Negative Symptom Scale
These similar scales that measure psychosis and depression are administered at every visit, and are done four times, once before the first arm and repeated after the end of the first arm three weeks later. Then after a 3 week washout the questionnaires are repeated, the 2nd arm started and at the end of 3 weeks, it is repeated again.
Measured: 4 times over 9 weeks
Tower of London
The Tower of London is a measure of cognitive functioning and is done four times, once before the first arm and repeated after the end of the first arm three weeks later. Then after a 3 week washout the measure is repeated, the 2nd arm started and at the end of 3 weeks, it is repeated again.
Measured: 4 times over 9 weeks
Trail Making Test
This is a measure of cognitive functioning and is done four times, once before the first arm and repeated after the end of the first arm three weeks later. Then after a 3 week washout the measure is repeated, the 2nd arm started and at the end of 3 weeks, it is repeated again.
Measured: Administered 4 times over 9 weeks
Letter-Number Test
It is a measure of cognitive functioning and is done four times, once before the first arm and repeated after the end of the first arm three weeks later. Then after a 3 week washout the measure is repeated, the 2nd arm started and at the end of 3 weeks, it is repeated again.
Measured: Administered 4 times over 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2013 (estimated)
- Study startJun 2011
- Primary completionMar 2012
- Study completionMar 2012
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 Adverse Mental/Physical Effects of Low Dose S. Tortuosum.Studies 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
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Woodbury, Michel, M.D.
- Collaborators
- PL Thomas & Co., Inc.
- Responsible party
- Principal investigator, Michel A. Woodbury, MD, Woodbury, Michel, M.D.
- Investigators
- Michel A Woodbury, MD, Principal investigator, Woodbury, MichelSimon Chiu, MD, Study chair, Western University, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01805518
- Sponsor's protocol ID
- NOEL 2011
- Status last verified
- Mar 2013
- First submitted
- 27 Jan 2013
- Last updated
- 6 Mar 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Chiu S, Gericke N, Farina-Woodbury M, Badmaev V, Raheb H, Terpstra K, Antongiorgi J, Bureau Y, Cernovsky Z, Hou J, Sanchez V, Williams M, Copen J, Husni M, Goble L. Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer's Dementia. Evid Based Complement Alternat Med. 2014;2014:682014. doi: 10.1155/2014/682014. Epub 2014 Oct 19.
PubMed 25389443
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 9 wk, Randomized, 2-blind, Placebo-controlled, 2X2 Cross-over Phase 1 Study of 25 mg of Scelectium Tortuosum (as Zembrin®) in Aged Normals to Find Effects on Mental, Emotional and Cognitive Safety Measures and Cytokines.
- ClinicalTrials.gov ID
- NCT01805518
- Acronym / sponsor ID
- NOEL 2011
- Keywords
- CNSVS, Tower of London, Letter-Number Test, Trail Making Test, Vital signs, Mood, Suicidal ideation, ECG
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Woodbury, Michel, M.D.
- Collaborators
- PL Thomas & Co., Inc.
- Study start
- Jun 2011
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 6 Mar 2013 (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.
Phosphodiesterase is a candidate for the Rx \& prevention of cognitive and psychotic disorders. Since caffeine targets primarily PDE4(Phosphodiesterase subtype 4), caffeine analogs have been developed to mimic the actions of caffeine's ability to inhibit PDE-a, PDE4, PDE5 and adenosine-2 (AD-2)but are limited by the side effects of insomnia and heightened anxiety. Sildenafil (PDE-5 inhibitor) fails to enhance cognition in schizophrenia.
The study of PDE-4 in cognition in Alzheimer's dementia and schizophrenia has been done using the PDE-4 prototypal compound, rolipram, which improves cognition in rodents. Rolipram reverses the memory deficits induced by amyloid fragment Abeta25-35 and Abeta1-40 peptide. In humans the frequent side effect of vomiting hampers translational research. The clinical trial of rolipram in multiple sclerosis was terminated prematurely due to serious adverse events with paradoxical increases in MRI MS-specific brain lesions. However, PDE-4 remains paradigm for cognition.
Another strategy is chemical moieties capable of antagonizing the PDE-4 through allosteric modulation, rather than direct competitive inhibition hoping to minimize adverse events while retaining the biological potencies and functional responses of PDE-4 Modulators. Dietary supplements with PDE-4 effects have advantages in that small investments are needed to adequately study them.
Pharmacologically active chemicals of Sceletium species are mesembrine-type alkaloids that have proven PDE-4 activity. The PDE-4D knockout mice have enhanced memory function mediated through hippocampal neurogenesis via phosphorylated cAMP response element binding protein (pCREB) signaling.
This study purpose is to delineate the relationship of PDE-4 and cognition in normals. pCREB is possibly the putative biomarker of PDE-4 response with CREB as effector signaling pathway of PDE-4. CREB is close to nuclear receptors represented by BDNF (Brain Derived Neurotrophic Factor) and PPAR (Peroxisome Proliferator Activating Receptor) complexes. CREB changes in neuronal plasticity are targets for pharmacological paradigms for cognitive enhancement. This study will use the scelectium tortuosum as manufactured as Zembrin®. The findings in control subjects will form the basis for designing future studies of Zembrin® in neurodegenerative disorders with marked cognitive impairment such as Alzheimer's Dementia and Parkinson's Disease.
Detailed description
- Contextual Background For the past decade, converging evidence suggests that targeting PD Phosphodiesterase for cognition represents novel heuristic approaches for development of dietary supplements and drug candidates for the treatment and prevention of cognitive and psychotic disorders.
- . The earlier findings on caffeine as the prototypal PD inhibitor targeting primarily PDE4 (Phosphodiesterase subtype 4) has stimulated synthesis of caffeine analogs to improve upon the pharmacokinetic profile and benefits/risk ratio.
- . The dual actions of caffeine as inhibitor of PDE-a, PDE4 and PDE5 and adenosine-2 (AD-2) antagonist, exerts multiple brain-behavior functions including sleep, cognition, memory and learning. It remains to be seen whether caffeine analogues live up the therapeutic potential in neurodegenerative diseases while bypassing the side effects of insomnia and heightened anxiety. Sildenafil (Viagra R) PDE-5 inhibitor indicated for erectile dysfunction (ED) fails to enhance cognition in schizophrenia
- . The full dosage range may not have been explored in the study with sildenafil. It is noteworthy that PDE-5 inhibition is related to NMDA (N-methyl-d-aspartic acid) glutamatergic modulation. In conducting a Pub Med search of recent studies point to the role of PDE-4 in diverse domains of cognition: memory, attention, executive function, recall, visual-spatial tasks. We find converging evidence targeting PDE-4 as the novel approach towards treating the cognitive deficits in Alzheimer dementia and schizophrenia
- . Most of the preclinical studies focus exclusively on the PDE-4 prototypal compound, rolipram. Rolipram improves memory consolidation, working memory and information processing in rodent species subjected to a variety of cognitive tasks: radial arm maze, passive avoidance, delayed arm water maze
- . A very recent study found that rolipram, reverses deficits induced by amyloid fragment Abeta25-35 and Abeta1-40 peptide in the Morris water maze and passive avoidance task
- . In preclinical screening of PDE-4 inhibitors, vomiting mediated via activating the area postema has been consistently noted. Tolerability and safety has hampered significantly the translation research in PDE-4 inhibitors. The clinical trial of rolipram in multiple sclerosis was terminated prematurely due to serious adverse events with paradoxical increases in MS-specific brain lesions identified by MRI
- . Notwithstanding the challenges in translational research, the molecular template of PDE-4 remains a highly viable paradigm for cognition. Drug Design has adopted another strategy in developing chemical moieties capable of antagonizing the PDE-4 pharmacological effects. Through allosteric modulation, rather than direct competitive inhibition at the catalytic site domain of PDE-4, the hope is to minimize the adverse events while retaining the biological potencies and functional responses relevant to the pharmacological activities of PDE-4 compounds.
- . The emergence of PDE-4 Modulators (PDE-4M) has attracted attention. Dietary supplements possessing the molecular templates and requirements in PDE-4 design strategy have added advantages in that preliminary clinical studies can be undertaken with a disproportionately small investment. If the preliminary results are favorable, strategic advances to GMP patented drug candidates are more predictable and confer less fiscal and clinical risks without compromising the efficacy stipulation in satisfying FDA criteria for phase II and Phase III trials. Our study the Zembrin® formulation of Scelectium Toruosum in cognition expands on an earlier study protocol which investigated the effects of Zembrin® in Generalized Anxiety Disorder (GAD). The pharmacologically active chemicals from the Sceletium species belong to mesembrine-type alkaloids; the structures are well characterized. Structure-activity relationship of the mesembrine-derivative alkaloids has been delineated in in-vitro assay of recombinant PDE-4 regarding the relative potencies in producing the functional responses. The IC50 of mesembrine-HCL is determined to be 20 microM
- . The PDE-4D knockout mice model provides evidence of enhanced memory function is mediated through hippocampal neurogenesis via phosphorylated cAMP response element binding protein (pCREB) signaling.
- . Microinfusion of lentiviral vectors carrying micro RNAs targeting the long-form of PDE4D isoforms directly into bilateral dentate gyrus of the hippocampus in the mice resulted in improved performance scores in object recognition test, water maze and radial arm maze. These considerations lead us to organize a pilot "proof-of-concept study" to delineate the relationship of PDE-4 and cognition in normal control subjects to validate the target of PDE-4 in modulating cognition functions in normal control subjects. It is noteworthy that none of the preliminary studies include measure of cAMP signaling in clinical subjects to correlate with brain-behavior interactions. With the availability of sensitive, reliable and valid ELISA method of assaying for pCREB, we consider it important to examine pCREB as the putative biomarker of PDE-4 response in clinical subjects treated with Zembrin®. There is emerging an increase of evidence in support of the construct that CREB as the effector signaling pathway of PDE-4, is the target of diverse classes of antidepressants
- . CREB is the late molecular partner to the family of nuclear receptors represented by BDNF (Brain derived neurotrophic factor) and PPAR (Peroxisome Proliferator Activating Receptor) complex
- . CREB reflects changes in neuronal plasticity and is sensitive to pharmacological paradigms for cognitive enhancement. CREB signaling integrates signal transduction from related neurotransmitters and neuromodulators besides PDE-4. Neuronal alpha-7 nicotinic receptor agonist A-582941 exerts its cognitive effects through interacting with phosphorylation of CREB pathway (13). The findings in control subjects will form the rational basis for designing controlled studies of Zembrin® in neurodegenerative disorders with marked cognitive impairment such as Alzheimer's Dementia and Parkinson's Disease.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Scelectium Tortuosum | Active comparator | Dietary Supplement: Scelectium TortuosumS Tortuosum |
| Sugar pill/placebo | Placebo comparator | –Sugar pill/placebo |
Who may qualify
- Ages
- 45 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Male or female Age: 45-65 Absence of DSM IV-R diagnosis As established by Mini-Psychiatric Interview HAM-D < 8 Body Mass Index (BMI) < 30.0 Not Suicidal
Key exclusion criteria (3 listed)
- Current (past 2 months) substance use disorder, Abuse of Caffeine Severe nicotine dependence Abuse of herbal and dietary supplements Current or planned pregnancy (for female) A major DSM IV-R psychiatric diagnosis.
- Recent myocardial ischemia or infarction, unstable angina, uncontrolled hypertension, poor glycemic control in Diabetes mellitus, Renal failure and serious renal diseases, Chronic active hepatitis, acute hepatitis, cirrhosis of liver, AIDS Active malignancy Neurological disorders: epilepsy Recent Traumatic brain injury Active suicidal risk Cerebrovascular disorders: recent stroke Inability to read nor write
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 |
|---|---|---|
| Scelectium TortuosumAlso: ZembrinOne arm has subjects 3 weeks on Scelectium Tortuosum 25gm po/d then 3 weeks off and then 3 weeks on Placebo. The other arm has subjects 3 weeks on placebo, then 3 weeks off and then 3 weeks on Scelectium Tortuosum 25mg po/d. | Dietary supplement | Scelectium Tortuosum |
Primary outcome
CNS Vital Signs
Time frame: 4 times over 9 weeks
CNS Vital Signs is a measure of cognitive functioning and is done four times, once before the first arm and repeated after the end of the first arm three weeks later. Then after a 3 week washout the measure is repeated, the 2nd arm started and at the end of 3 weeks, it is repeated again.
10 secondary outcomes
Side effect questionnaire
Time frame: 4 times over 9 weeks
Columbia Suicide Scale
Time frame: 4 times over 9 weeks
ECG
Time frame: 4 times over 9 weeks
Vital Signs
Time frame: 4 times over 9 weeks
Physical Exam
Time frame: 4 times over 9 weeks
Urine
Time frame: 4 collections over 9 weeks
Brief Psychiatric Scale and Positive and Negative Symptom Scale
Time frame: 4 times over 9 weeks
Tower of London
Time frame: 4 times over 9 weeks
Trail Making Test
Time frame: Administered 4 times over 9 weeks
Letter-Number Test
Time frame: Administered 4 times over 9 weeks
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 6 Mar 2013.
- Derived from this study: PubMed 25389443Chiu S, Gericke N, Farina-Woodbury M, Badmaev V, Raheb H, Terpstra K, Antongiorgi J, Bureau Y, Cernovsky Z, Hou J, Sanchez V, Williams M, Copen J, Husni M, Goble L. Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer's Dementia. Evid Based Complement Alternat Med. 2014;2014:682014. doi: 10.1155/2014/682014. Epub 2014 Oct 19.
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.
Michel A Woodbury, MD principal investigator
Woodbury, Michel
Simon Chiu, MD study chair
Western University, Canada
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 Scelectium Tortuosum in people with Adverse Mental/Physical Effects of Low Dose S. Tortuosum., run by Woodbury, Michel, M.D. at 1 site in Puerto Rico.
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 1 inclusion and 3 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 6 Mar 2013. 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 Puerto Rico. 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?
CNS Vital Signs (time frame: 4 times over 9 weeks). 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 NCT01805518, 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 6 Mar 2013.