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Safety Study of the Effect of Scelectium Tortuosum (as Zembrin®)in Aged Normals

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ClinicalTrials.gov Identifier: NCT01805518
Recruitment Status : Completed
First Posted : March 6, 2013
Last Update Posted : March 6, 2013
Sponsor:
Collaborator:
PL Thomas & Co., Inc.
Information provided by (Responsible Party):
Michel A. Woodbury, MD, Woodbury, Michel, M.D.

Brief 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 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.


Condition or disease Intervention/treatment Phase
Adverse Mental/Physical Effects of Low Dose S. Tortuosum. Dietary Supplement: Scelectium Tortuosum Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
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.
Study Start Date : June 2011
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012

Arm Intervention/treatment
Active Comparator: Scelectium Tortuosum
S Tortuosum
Dietary Supplement: Scelectium Tortuosum

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.

Other Name: Zembrin

Placebo Comparator: Sugar pill/placebo
Sugar pill/placebo



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Side effect questionnaire [ Time Frame: 4 times over 9 weeks ]
    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.

  2. Columbia Suicide Scale [ Time Frame: 4 times over 9 weeks ]
    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.

  3. ECG [ Time Frame: 4 times over 9 weeks ]
    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.

  4. Vital Signs [ Time Frame: 4 times over 9 weeks ]
    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.

  5. Physical Exam [ Time Frame: 4 times over 9 weeks ]
    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.

  6. Urine [ Time Frame: 4 collections over 9 weeks ]
    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.

  7. Brief Psychiatric Scale and Positive and Negative Symptom Scale [ Time Frame: 4 times over 9 weeks ]
    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.

  8. Tower of London [ Time Frame: 4 times over 9 weeks ]
    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.

  9. Trail Making Test [ Time Frame: Administered 4 times over 9 weeks ]
    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.

  10. Letter-Number Test [ Time Frame: Administered 4 times over 9 weeks ]
    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.


Other Outcome Measures:
  1. Cytokines [ Time Frame: 4 measures over 9 weeks ]
    Blood serum taken 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.

  2. Blood work-up [ Time Frame: 4 collections over 9 weeks ]
    Blood for complete metabolic panel, CBC, C-Reactive Protein is taken 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 is taken again, the 2nd arm started and at the end of 3 weeks, it is repeated again.

  3. Hamilton Mood questionnaire [ Time Frame: 4 visits over 9 weeks ]
    Depression via the Hamilton Mood Questionnaire is assessed in 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 measure is repeated, the 2nd arm started and at the end of 3 weeks, it is repeated again.



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Ages Eligible for Study:   45 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01805518


Locations
Puerto Rico
Michel A. Woodbury, MD
San Juan, Puerto Rico, 00918
Sponsors and Collaborators
Woodbury, Michel, M.D.
PL Thomas & Co., Inc.
Investigators
Principal Investigator: Michel A Woodbury, MD Woodbury, Michel
Study Chair: Simon Chiu, MD University of Western Ontario, Canada

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Michel A. Woodbury, MD, Priciple Investigator, Woodbury, Michel, M.D.
ClinicalTrials.gov Identifier: NCT01805518     History of Changes
Other Study ID Numbers: NOEL 2011
First Posted: March 6, 2013    Key Record Dates
Last Update Posted: March 6, 2013
Last Verified: March 2013

Keywords provided by Michel A. Woodbury, MD, Woodbury, Michel, M.D.:
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