Study of the Anxiolytic Effects of Aframomum Seed Extract in Elderly People

Effects of a Plant Extract Modulating the Endocannabinoid System and Its Anxiolytic Capacity on Elderly People in Situations of Stress or Anxiety

The goal of this pilot clinical trial is to evaluate if one specific botanical extract from Grains of Paradise works to induce anxiolytic effect in adult people in stress or anxiety situations It will also learn about the extract's positive effects on sleep and mood. The main questions it aims to answer are:

Does botanical extract exert an anxiolytic effect on the participants under stress or anxiety circumstances? Does botanical extract promote positive effects on Mood and nocturnal sleep? Does botanical extract influence body parameters like Blood pressure, inflammatory indicators or stress hormones? Researchers will compare tree doses of botanical extract (50,100 or 150mg) to a placebo (a look-alike substance that contains no herbal product) to see if herbal extract support anxiolytic effect.

Participants will:

Take herbal extract or a placebo daily for 3 days. Visit the clinic two times: at the start of the study (day0) and to the end of the study (Day +2)for checkups and tests.

Keep a diary with questions about their activities, daily foods and physicals perceptions.

Study Overview

• Status: Completed
• Conditions: Situational Anxiety
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Vanizem

Detailed Description

The present randomized, double-blind, placebo-controlled crossover trial aims to evaluate the effects of standardized aframomum melegueta seed extract (AME) supplementation on anxiety, mood and sleep quality in healthy men and women experiencing anxious situations. A total of 37 participants were randomly assigned to either AME-first groups or placebo-first group; participants were taken 50, 100 or 150 mg of either AME or matched placebo peels daily for three days. This period is followed by a 1 week washout period at the beginning of which all participants will stop the assigned intervention. After this washout the participants will start their crossover intervention. All Participants were instructed to follow a standardized training program throughout the study, including washout periods to maintain uniformity in physical activity and reduce the effect that exercise can have on stress management. The effects of supplement AME doses compared with a placebo, were evaluated using measures to assess anxiety [The Hamilton Anxiety Scale (HAM-A)], mood [Adapted Profile Mood State (POMS)], sleep quality [Sleep Evaluation Questionnaire (LSEQ) and Pittsburgh Sleep Quality Index (PSQI)]. In addition, some physiological (Blood pressure and heart rate variability), biochemical (minerals, hepatic enzymes and inflammatory biomarkers) and hematological variables (Complete cell count) were determined. Testing was completed at the beginning (Day0) and at the end (Day2) of the supplementation periods with the extract and placebo products to assess acute effects following 3 days of daily use.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Alicante, Spain, 3005
    • Kinetic perfomance SL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female between 40 and 50 year of age;
• Healthy people with moderate anxiety: HAM-A score in a range between 18 and 24;
• Subject able and willing to participate to the study by complying with the protocol procedures as confirmed by his dated and signed informed consent form;

Exclusion Criteria:

• Score greater than 20 points on the Hamilton Depression Rating Scale (HDRS);
• Receiving medical treatment for anxiety, stress or depression;
• Drugs and alcohol dependence;
• Serious personality disorders that may interfere with participation in the study (psychosis, intense suicidal ideation, etc.);
• In the case of women, having the intention of becoming pregnant;
• Epileptic disorders;
• Liver disorders (cirrhosis, hepatitis, etc.);
• Professional athletes or those who frequently engage in extreme physical activities;
• Impossibility of completing the intervention period due to external factors;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Pill of Food grade Maltodextrin 12 . Once daily for three days.	Dietary supplement: Placebo; Food grade Maltodextrin 12
Experimental: Vanizem 50mg; Pill of Aframomum melegueta extract 50 mg with Food grade Maltodextrin 12 . Once daily for three days.	Dietary supplement: Vanizem; Aframomum melegueta seed extract standardized to 10% of total Vanilloid and at least 1.5% of 6-paradol
Experimental: Vanizem 100mg; Pill of Aframomum melegueta extract 100 mg with Food grade Maltodextrin 12 . Once daily for three days.	Dietary supplement: Vanizem; Aframomum melegueta seed extract standardized to 10% of total Vanilloid and at least 1.5% of 6-paradol
Experimental: Vanizem 150mg; Pill of Aframomum melegueta extract 150 mg with Food grade Maltodextrin 12 . Once daily for three days.	Dietary supplement: Vanizem; Aframomum melegueta seed extract standardized to 10% of total Vanilloid and at least 1.5% of 6-paradol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hamilton Anxiety Rating Scale (HAM-A) score	Change in HAM-A score for Vanizem group compared to placebo control group. 14-items questionnaire reflecting 13 categories of anxiety-related symptom to measure anxiety.	At baseline (day 0) and after intake period (day 2+)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Profile of Mood States (POMS) score	Change in POMS score for Vanizem group compared to placebo control group. 65-items to evaluate short-term emotional states and represent six subscales assessing tension-anxiety, depression, anger-hostility, fatigue, confusion-bewilderment, and vigor-activity.	At baseline (day 0) and after intake period (day 2+)
Change in Pittsburgh Sleep Quality Index (PSQI) score	Change in PSQI score for Vanizem group compared to placebo control group. 24-items measuring seven dimensions that can be broadly categorized into sleep efficiency factors (sleep quality, sleep latency, sleep duration, and habitual sleep efficiency) and sleep disturbance factors (sleep disturbance, use of sleep medications, and daytime disturbance).	At baseline (day 0) and after intake period (day 2+)
Change in Leeds Sleep Evaluation Questionnaire (LSEQ) score. 10-items evaluating four domains: ease of initiating sleep, quality of sleep, ease of waking, and behavior following wakefulness.	Change in LSEQ score for Vanizem group compared to placebo control group.	At baseline (day 0) and after intake period (day 1+ and day 2+)
Change in Heart Rate Variability (HRV)	Change HRV score for Vanizem group compared to placebo control group. Heart rate variability measured as interbeat intervals (ms) has been collected with POLAR H10+ heart rate bands during sleeping hours.	At baseline (day 0) and after intake period (day 1+ and day 2+)
Change in blood pressure score	Change in systolic and diastolic blood pressure (mmHg) for Vanizem group compared to placebo control group.	At baseline (day 0) and after intake period (day 2+)
Change in blood cells count	Changes in a neutrophils, lymphocyte, monocyte, eosinophil, basophil, platelet and red blood cell counts (Cells/mcL) for Vanizem group compared to placebo control group.	At baseline (day 0) and after intake period (day 2+)
Change in blood minerals levels	Changes in Magnesium (mmol/L) and Zinc (mcmol/L) levels for Vanizem group compared to placebo control group.	At baseline (day 0) and after intake period (day 2+)
Change in blood electrolyte levels	Changes in Sodium and Chloride levels (mEq/L) for Vanizem group compared to placebo control group.	At baseline (day 0) and after intake period (day 2+)
Change in serum hepatic enzymes	Changes in gamma-glutamyltransferase (GGT), serum glutamic pyruvic transaminase (GPT), serum glutamic oxaloacetic transaminase (GOT) and alkaline phosphatase (AP) levels (IU/L) for Vanizem group compared to placebo control group.	At baseline (day 0) and after intake period (day 2+)
Change proinflammatory serum biomarkers	Changes in interleukin-1, interleukin-6, interleukin-8 and tumour necrosis factor alpha levels (pg/mL) for Vanizem group compared to placebo control group.	At baseline (day 0) and after intake period (day 2+)
Change in protein serum biomarker of inflammation	Changes in c-reactive protein levels (mg/L) for Vanizem group compared to placebo control group.	At baseline (day 0) and after intake period (day 2+)
Change in serum biomarker of stress	Changes in cortisol (mcg/dL) levels for Vanizem group compared to placebo control group.	At baseline (day 0) and after intake period (day 2+)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in body composition	Changes in body fat mass (BFM), body fat percentage (%BF), lean muscle mass (LMM) and percentage of lean muscle mass (%LMM) for Vanizem group compared to placebo control group. Measurements will be assessed using multifrequency bioelectrical impedance analysis (BIA).	At baseline (day 0) and after intake period (day 2+)
Changes in body weight	Changes in body weight (kg) for Vanizem group compared to placebo control group.	At baseline (day 0) and after intake period (day 2+)
Changes in body mass index (BMI)	BMI for Vanizem group compared to placebo control group. Weight (kg) and height (cm) will be combined to report BMI in (kg/cm^2).	At baseline (day 0) and after intake period (day 2+)

Collaborators and Investigators

• Sponsor: Nektium Pharma SL
• Collaborators: Kinetic performance
• Investigators: Principal Investigator: Laura López-Rios, PhD, Nektium Pharma SL

Publications and helpful links

General Publications

• Umukoro S. and Aladeokin A. C., Therapeutic effects of grains of paradise (aframomum melegueta) seeds Nuts and Seeds in Health and Disease Prevention, 2011, Academic Press, Cambridge, MA, USA, 535-543.
• Ilic NM, Dey M, Poulev AA, Logendra S, Kuhn PE, Raskin I. Anti-inflammatory activity of grains of paradise (Aframomum melegueta Schum) extract. J Agric Food Chem. 2014 Oct 29;62(43):10452-7. doi: 10.1021/jf5026086. Epub 2014 Oct 20.
• Ogwu, M.C., Dunkwu-Okafor, A., Omakor, I.A., Izah, S.C. (2024). Medicinal Spice, Aframomum melegueta: An Overview of the Phytochemical Constituents, Nutritional Characteristics, and Ethnomedicinal Values for Sustainability. In: Izah, S.C., Ogwu, M.C., Akram, M. (eds) Herbal Medicine Phytochemistry. Reference Series in Phytochemistry. Springer, Cham. https://doi.org/10.1007/978-3-031-21973-3_72-1
• Umukoro S, Ashorobi RB. Further studies on the antinociceptive action of aqueous seed extract of Aframomum melegueta. J Ethnopharmacol. 2007 Feb 12;109(3):501-4. doi: 10.1016/j.jep.2006.08.025. Epub 2006 Sep 3.
• Ford JL, Ildefonso K, Jones ML, Arvinen-Barrow M. Sport-related anxiety: current insights. Open Access J Sports Med. 2017 Oct 27;8:205-212. doi: 10.2147/OAJSM.S125845. eCollection 2017.
• Halson SL, Juliff LE. Sleep, sport, and the brain. Prog Brain Res. 2017;234:13-31. doi: 10.1016/bs.pbr.2017.06.006. Epub 2017 Jul 17.
• Patel S, Hill MN, Cheer JF, Wotjak CT, Holmes A. The endocannabinoid system as a target for novel anxiolytic drugs. Neurosci Biobehav Rev. 2017 May;76(Pt A):56-66. doi: 10.1016/j.neubiorev.2016.12.033.
• Batista LA, Gobira PH, Viana TG, Aguiar DC, Moreira FA. Inhibition of endocannabinoid neuronal uptake and hydrolysis as strategies for developing anxiolytic drugs. Behav Pharmacol. 2014 Sep;25(5-6):425-33. doi: 10.1097/FBP.0000000000000073.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Actual): April 12, 2023
• Study Completion (Actual): May 20, 2023

Study Registration Dates

• First Submitted: June 12, 2024
• First Submitted That Met QC Criteria: June 14, 2024
• First Posted (Actual): June 17, 2024

Study Record Updates

• Last Update Posted (Actual): July 1, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Anxiety; Herbal extract; Aframomum melegueta seed; FAAH inhibitor; Quality sleep; Grains of paradise
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders
• Other Study ID Numbers: AME_HCT_2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No