A Study to Evaluate the Effect of EnXtra® and EnXtra® + Caffeine on Mental Alertness and Fatigue in Healthy Individuals
NCT Number: NCT06560008
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Fatigue|Mental Alertness
Interventions: DIETARY_SUPPLEMENT: EnXtra® (300 mg) + Placebo (300 mg)|DIETARY_SUPPLEMENT: Caffeine (200 mg) + Placebo (300 mg)|DIETARY_SUPPLEMENT: EnXtra® (300 mg) + Caffeine (200 mg)|DIETARY_SUPPLEMENT: Placebo (MCC 300 mg) + Placebo (300 mg)
Sponsor: Vedic Lifesciences Pvt. Ltd.
Collaborators: Enovate Biolife Pvt Ltd
Sex: ALL
Age: ADULT
Enrollment: 128
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: OTHER
Start Date: 2024-08-19
Completion Date: 2025-06-19
Locations: New Manak Healcare Hospital, Navi Mumbai, Maharashtra, 400706, India|Dr. Joshi's Neurotrauma Centre, Thāne, Maharashtra, 400601, India|Gurukrupa Hospital, Thāne, Maharashtra, 400601, India|Kalpana Hospital, Thāne, Maharashtra, 400601, India

Summary:
Acute Stage: The present study is a randomized, double-blind, placebo-controlled, single-dose, 4-way, cross-over, study. Approximately not more than 170 individuals will be screened and considering a screening failure rate of 25%, approximately 128 individuals will be randomized in a ratio of 1:1:1:1 to receive one of the IPs and will be assigned a unique randomization code. In this stage, approximately 114 individuals will complete the study, after accounting for a dropout/withdrawal rate of 15%. The intervention duration is 4 days \[1 (single dose) x 4 periods\].

Sub-Acute Stage: The present study is a randomized, double-blind, placebo-controlled, 4 arms, parallel study. In this stage, approximately 112 individuals will be re-randomized in a ratio of 1:1:1:1 to receive one of the IPs and will be assigned a unique randomization code. Each group will have not less than 24 completed participants after accounting for a dropout/withdrawal rate of 15%. The intervention duration is 28 days.

Primary Outcome Measures: To determine the effect of EnXtra® and EnXtra® + Caffeine on alertness score as assessed by the change in the Jin Fan Alertness score as compared to placebo and caffeine in Acute stage., The Attention Network Test (ANT) is an assessment tool to evaluate efficacy of three distinct attention networks: alerting, orienting, and executive networks.

Alerting effect = mean Response Time (RT) (correct no cue) - mean RT (correct centre cue) Orienting effect = mean RT (correct centre cue) - mean RT (correct spatial cue) Conflict effect = mean RT (correct incongruent) - mean RT (correct congruent) Correct: correctness of response No cue condition: participant does not receive any cue before the target stimulus appears.

Spatial cue is usually presented in the form of an arrow, pointing in the location where the target stimulus will show up.

Centre cue condition, A cue appears at the screen's center just before the target stimulus.

Incongruent: The target stimulus is flanked by distractors oriented in the opposite direction.

Congruent: The target stimulus is flanked by distractor stimuli oriented in the same direction., Day 0 at 0, 1, 3 and 5 hours ± 15 minutes post IP|To determine the effect of EnXtra® and EnXtra® + Caffeine on alertness score as assessed by the change in the Jin Fan Alertness score as compared to placebo and caffeine in Acute stage., The Attention Network Test (ANT) is an assessment tool to evaluate efficacy of three distinct attention networks: alerting, orienting, and executive networks.

Alerting effect = mean Response Time (RT) (correct no cue) - mean RT (correct centre cue) Orienting effect = mean RT (correct centre cue) - mean RT (correct spatial cue) Conflict effect = mean RT (correct incongruent) - mean RT (correct congruent) Correct: correctness of response No cue condition: participant does not receive any cue before the target stimulus appears.

Spatial cue is usually presented in the form of an arrow, pointing in the location where the target stimulus will show up.

Centre cue condition, A cue appears at the screen's center just before the target stimulus.

Incongruent: The target stimulus is flanked by distractors oriented in the opposite direction.

Congruent: The target stimulus is flanked by distractor stimuli oriented in the same direction., Day 5 at 0, 1, 3 and 5 hours ± 15 minutes post IP|To determine the effect of EnXtra® and EnXtra® + Caffeine on alertness score as assessed by the change in the Jin Fan Alertness score as compared to placebo and caffeine in Acute stage., The Attention Network Test (ANT) is an assessment tool to evaluate efficacy of three distinct attention networks: alerting, orienting, and executive networks.

Alerting effect = mean Response Time (RT) (correct no cue) - mean RT (correct centre cue) Orienting effect = mean RT (correct centre cue) - mean RT (correct spatial cue) Conflict effect = mean RT (correct incongruent) - mean RT (correct congruent) Correct: correctness of response No cue condition: participant does not receive any cue before the target stimulus appears.

Spatial cue is usually presented in the form of an arrow, pointing in the location where the target stimulus will show up.

Centre cue condition, A cue appears at the screen's center just before the target stimulus.

Incongruent: The target stimulus is flanked by distractors oriented in the opposite direction.

Congruent: The target stimulus is flanked by distractor stimuli oriented in the same direction., Day 10 at 0, 1, 3 and 5 hours ± 15 minutes post IP|To determine the effect of EnXtra® and EnXtra® + Caffeine on alertness score as assessed by the change in the Jin Fan Alertness score as compared to placebo and caffeine in Acute stage., The Attention Network Test (ANT) is an assessment tool to evaluate efficacy of three distinct attention networks: alerting, orienting, and executive networks.

Alerting effect = mean Response Time (RT) (correct no cue) - mean RT (correct centre cue) Orienting effect = mean RT (correct centre cue) - mean RT (correct spatial cue) Conflict effect = mean RT (correct incongruent) - mean RT (correct congruent) Correct: correctness of response No cue condition: participant does not receive any cue before the target stimulus appears.

Spatial cue is usually presented in the form of an arrow, pointing in the location where the target stimulus will show up.

Centre cue condition, A cue appears at the screen's center just before the target stimulus.

Incongruent: The target stimulus is flanked by distractors oriented in the opposite direction.

Congruent: The target stimulus is flanked by distractor stimuli oriented in the same direction., Day 15 at 0, 1, 3 and 5 hours ± 15 minutes post IP|To determine the effect of EnXtra® and EnXtra® + Caffeine on alertness score as assessed by the change in the Jin Fan Alertness score as compared to placebo and caffeine in Sub-acute stage., The Attention Network Test (ANT) is an assessment tool to evaluate efficacy of three distinct attention networks: alerting, orienting, and executive networks.

Alerting effect = mean Response Time (RT) (correct no cue) - mean RT (correct centre cue) Orienting effect = mean RT (correct centre cue) - mean RT (correct spatial cue) Conflict effect = mean RT (correct incongruent) - mean RT (correct congruent) Correct: correctness of response No cue condition: participant does not receive any cue before the target stimulus appears.

Spatial cue is usually presented in the form of an arrow, pointing in the location where the target stimulus will show up.

Centre cue condition, A cue appears at the screen's center just before the target stimulus.

Incongruent: The target stimulus is flanked by distractors oriented in the opposite direction.

Congruent: The target stimulus is flanked by distractor stimuli oriented in the same direction., Day 20 at 0 hours post IP|To determine the effect of EnXtra® and EnXtra® + Caffeine on alertness score as assessed by the change in the Jin Fan Alertness score as compared to placebo and caffeine in Sub-acute stage., The Attention Network Test (ANT) is an assessment tool to evaluate efficacy of three distinct attention networks: alerting, orienting, and executive networks.

Alerting effect = mean Response Time (RT) (correct no cue) - mean RT (correct centre cue) Orienting effect = mean RT (correct centre cue) - mean RT (correct spatial cue) Conflict effect = mean RT (correct incongruent) - mean RT (correct congruent) Correct: correctness of response No cue condition: participant does not receive any cue before the target stimulus appears.

Spatial cue is usually presented in the form of an arrow, pointing in the location where the target stimulus will show up.

Centre cue condition, A cue appears at the screen's center just before the target stimulus.

Incongruent: The target stimulus is flanked by distractors oriented in the opposite direction.

Congruent: The target stimulus is flanked by distractor stimuli oriented in the same direction., Day 48 at 1, 3 and 5 hours ± 15 minutes post IP
Secondary Outcome Measures: To determine the effect of EnXtra® and EnXtra® + Caffeine on Eye-hand coordination as assessed by Nine hole peg test (NHPT) as compared to placebo and caffeine in Acute stage., The NHPT assesses eye-hand coordination in individuals. This study focuses on the dominant hand's performance.

Metrics recorded for assessment:

Moving Duration - 1: Time to move the first peg from the holder to the board, indicating initial movement speed and fluidity.

First Peg Selection - 1: Time from the start of the test until the first peg is picked up, indicating readiness and initial response speed.

Transport Drops - 1: Number of times the first peg is dropped during transport, assessing precision and control.

Moving Duration - 2: Similar to Moving Duration - 1 for the second peg, providing insight into consistency and endurance over multiple attempts.

First Peg Selection - 2: Time taken to select the first peg again, measuring sustained attention and readiness.

Transport Drops - 2: No. of drops during the second transport attempt, evaluating precision and control.

An increase in moving duration indicates a decline in eye-hand coordination speed., Day 0; Day 5; Day 10; Day 15 - 0, 1, 3 & 5 hours ±15 minutes post IP|To determine the effect of EnXtra® and EnXtra® + Caffeine on Eye-hand coordination as assessed by Nine hole peg test (NHPT) as compared to placebo and caffeine in Sub-acute stage., The NHPT assesses eye-hand coordination in individuals. This study focuses on the dominant hand's performance.

Metrics recorded for assessment:

Moving Duration - 1: Time to move the first peg from the holder to the board, indicating initial movement speed and fluidity.

First Peg Selection - 1: Time from the start of the test until the first peg is picked up, indicating readiness and initial response speed.

Transport Drops - 1: Number of times the first peg is dropped during transport, assessing precision and control.

Moving Duration - 2: Similar to Moving Duration - 1 for the second peg, providing insight into consistency and endurance over multiple attempts.

First Peg Selection - 2: Time taken to select the first peg again, measuring sustained attention and readiness.

Transport Drops - 2: No. of drops during the second transport attempt, evaluating precision and control.

An increase in moving duration indicates a decline in eye-hand coordination speed., Day 20 - 0 hours, Day 48 - 1, 3 & 5 hours ±15 minutes post IP|To determine the effect of EnXtra® and EnXtra® + Caffeine on Sustained attention as assessed by Continuous Performance test (CPT) as compared to placebo and caffeine in acute stage., This task is primarily designed to measure selective and sustained attention, with some capacity to assess impulsivity to a lesser degree. CPT measures sustained attention and response time. Sustained attention is measured by assessing how well participants can maintain their focus throughout the test. The response time is measured by calculating the average time it takes for a participant to respond to target stimuli. In the CPT, a decline in sustained attention is often reflected in increased response times and greater variability. This can occur as participants become fatigued or distracted over time, leading to slower and less consistent responses.Hence, a long response time may suggest cognitive slowing and/or impairment., Day 0; Day 5; Day 10; Day 15 - 0, 1, 3 & 5 hours ±15 minutes post IP|To determine the effect of EnXtra® and EnXtra® + Caffeine on Sustained attention as assessed by Continuous Performance test (CPT) as compared to placebo and caffeine in sub-acute stage., This task is primarily designed to measure selective and sustained attention, with some capacity to assess impulsivity to a lesser degree. CPT measures sustained attention and response time. Sustained attention is measured by assessing how well participants can maintain their focus throughout the test. The response time is measured by calculating the average time it takes for a participant to respond to target stimuli. In the CPT, a decline in sustained attention is often reflected in increased response times and greater variability. This can occur as participants become fatigued or distracted over time, leading to slower and less consistent responses.Hence, a long response time may suggest cognitive slowing and/or impairment., Day 20 - 0 hours, Day 48 - 1, 3 & 5 hours ±15 minutes post IP|To determine the effect of EnXtra® and EnXtra® + Caffeine on Fatigue as assessed by the change in the Samn-Perelli fatigue scale (SPS) compared to placebo and caffeine in acute stage., SPS is a uni-dimensional 7-point scale that was specifically developed to estimate fatigue in pilots. It is also a 7-point Likert-type scale of subjective fatigue ranging from 1 = "fully alert, wide awake, extremely peppy" to 7 = "completely exhausted, unable to function effectively, ready to drop., Day 0; Day 5; Day 10; Day 15 - 0, 1, 3 & 5 hours ±15 minutes post IP|To determine the effect of EnXtra® and EnXtra® + Caffeine on Fatigue as assessed by the change in the Samn-Perelli fatigue scale (SPS) compared to placebo and caffeine in sub-acute stage., SPS is a uni-dimensional 7-point scale that was specifically developed to estimate fatigue in pilots. It is also a 7-point Likert-type scale of subjective fatigue ranging from 1 = "fully alert, wide awake, extremely peppy" to 7 = "completely exhausted, unable to function effectively, ready to drop., Day 20 - 0 hours, Day 48 - 1, 3 & 5 hours ±15 minutes post IP|To determine the safety of EnXtra® and EnXtra® + Caffeine as assessed by the Complete Blood Count - CBC, The CBC typically includes:

1. WBC total and differential count (Reference range: 4 - 10 10\^3/microlitres)-
2. erythrogram (RBC count (Reference range: 4.5 - 5.5 10\^6/microlitres), determination of hemoglobin (Hb) (Reference range: 12.0 - 17.0 g/dL) and hematocrit (Reference range: 40 - 50 %), and indices calculation (mean corpuscular volume (MCV) (Reference range: 83-101 fL), mean corpuscular hemoglobin (MCH) (Reference range: 27 - 32 pg), mean corpuscular hemoglobin concentration (MCHC) (Reference range: 31.5 - 34.5 g/dL), and red cell distribution width (RDW) (Reference range: 11.6 - 14.0 %) and;
3. platelet count (Reference range: 7.4 - 11.4 fL) indices calculation, Screening and Day 48|To determine the safety of EnXtra® and EnXtra® + Caffeine as assessed by the Liver Function Tests (LFT), The liver function tests (LFT) typically include alanine transaminase (ALT) (Reference range: 9-72 IU/L) and aspartate transaminase (AST) (Reference range: 14-59 IU/L), alkaline phosphatase (ALP) (Reference range: 38-126 U/L). These tests aid in identifying areas of liver damage and, based on the elevation pattern, contribute to forming a differential diagnosis., Screening and Day 48|To determine the safety of EnXtra® and EnXtra® + Caffeine as assessed by the Kidney Function Tests (KFT), The kidney function tests (KFT) typically include serum creatinine (Reference range: 0.5 - 1.4 mg/dL) and blood urea nitrogen (BUN) (Reference range: 7-23 mg/dL). These tests help to evaluate renal function and detect the presence of kidney disease., Screening and Day 48