Efficacy and Safety of a Proprietary Blend of Ashwagandha Root Extract (Aqueous) in Adult Men and Women With High Stress and Anxiety: A Randomized, Double-blind, Three-arm, Parallel, Placebo-controlled Study

This is a Multi-center, Multi-national, Prospective, Randomized, Double-Blind, Placebo- Controlled three arm study to evaluate the efficacy and safety of a Proprietary Blend of Ashwagandha Root Extract (Aqueous) in Adult Men and Women with High Stress and Anxiety. All eligible subjects who meet the Inclusion and Exclusion criteria will be part of the study. Subjects will be informed about the purpose of the study and signed informed consent will be taken. Subjects will be randomized to either one of the three treatment arms. Subjects will then be asked to either take one capsule containing the proprietary blend of Ashwagandha root extract or Ashwagandha root extract or Placebo orally twice daily with a glass of water for 8 weeks. The primary objective is to compare the efficacy of a proprietary blend of Ashwagandha root extract in adults experiencing stress and anxiety. The secondary objective is to compare the safety of a proprietary blend versus KSM-66 versus Placebo in adults experiencing stress and anxiety.

To qualify for the study, participants must be aged between 18 to 55 years experiencing signs and symptoms suggestive of stress (e.g., difficulty, concentrating, physical exhaustion, anxiety, restlessness, insomnia, headache, fatigue, loss of appetite, worry, sweating, mental confusion, etc.).

In this study, a maximum of 51 patients will be enrolled and the goal is to complete the study with at least 45 patients.

After signing this consent form, participants will answer questions regarding their medical history, including any medications they are taking. Physical exams with vital signs (pulse, temperature, sitting blood pressure and respiratory rate) will be performed at both visits by a professional trained to perform this testing. It may be a Nurse (RN or LPN), Phlebotomist, or Medical Doctor.

A blood sample will be required from subjects. Subject's right or left arm will be used as the blood draw site, requiring a 5mL sample.e blood will be analyzing Cortisol level. These blood draws will be administered by a professional trained to perform this testing. It may be a Nurse (RN or LPN), Phlebotomist or Medical Doctor.

A two-page Hamilton Anxiety Rating Scale (HAM-A) Test and Perceived Stress Scale (PSS) will be given and administered as self-assessment.

All eligible participants, will be given the required quantity of the study medication for self-administration, sufficient till the Visit 3- End of study visit, 8 weeks ± 4 Days. Participants will be randomized to either one of the three treatment arms.

Participants will be instructed to take one capsule of study medication to which they are randomized twice daily, with ambient temperature water for 8 weeks at home. Participants will be asked to visit the site for Visit 2 (4 weeks ± 4 Days), Visit 3 (8 weeks ± 4 Days). Adverse events and concomitant medication will be recorded throughout the study. Participants will be asked to get used and unused study medications and their subject diaries in this visit. All the participants will be asked to continue their routine diet and physical activities during the whole study period.

The primary end point is mean change in serum cortisol level from baseline. The secondary end points are Perceived Stress Scale (PSS) questionnaire, Hamilton Anxiety Rating Scale (HAM-A) questionnaire, Profile of Mood States (POMS, abbreviated version) questionnaire, Oxford Happiness Questionnaire from baseline. The safety end points are the Number and proportion of Treatment-Emergent Adverse Events (TEAEs) over 8 weeks and the Number and proportion of Treatment-Emergent Serious Adverse Events (TESAE) over 8 weeks.

Eligibility Criteria:
Inclusion Criteria:

1. Adults (male and female) aged between 18 and 65 years.
2. Experiencing signs and symptoms suggestive of stress (e.g., difficulty, concentrating, physical exhaustion, anxiety, restlessness, insomnia, headache, fatigue, loss of appetite, worry, sweating, mental confusion, etc.).
3. Hamilton Anxiety Rating Scale (HAM-A) total score between 14 and 30 at the screening/randomization visit.
4. Perceived Stress Scale (PSS) score ≥13 at the screening/randomization visit.
5. BMI between 20 and 35.
6. No plan to commence new treatments over the study period.
7. Medication-free (any medications are known to affect stress and anxiety) for at least 4 weeks. Use of analgesics (once a week) or contraceptive pills are permissible.
8. Must have the ability and willingness to sign an informed consent and to comply with all study procedures.

Exclusion Criteria:

1. Patients receiving any of the medications known to affect stress and anxiety (corticosteroids, antidepressants, antipsychotics, mood stabilizers, and anti-epileptic medications) during 4 weeks prior to screening.
2. Patients having a total score of less than 14 on HAM-A at screening.
3. Patients currently (or within the past 4 weeks prior to screening) taking any over-the-counter use of herbal extracts such as Ginkgo Biloba, St. John's Wort, Omega-3, etc.
4. Patients with a depressive episode, suicidal tendency, panic disorder, social phobia, obsessive-compulsory disorder; alcohol dependency; schizophrenia, and mania.
5. Patients with known post-traumatic stress disorder (PTSD) and Generalized Anxiety Disorder (GAD).
6. Patients who have an established practice of meditation and relaxation techniques for three or more months.
7. Patients with known clinically significant acute unstable hepatic, renal, cardiovascular, or respiratory disease that will prevent participation in the study.
8. Patients with a history of alcohol, tobacco dependence, or any substance abuse.
9. Pregnant and lactating women or suspected to be pregnant.
10. Patients with known hypersensitivity to Ashwagandha.
11. Patients who had participated in other clinical trials during the previous 3 months.
12. Patients who have any clinical condition, according to the investigator who does not allow safe fulfilment of clinical trial protocol.