Pilot Trial for Health Products on Mood and Sleep Quality

Official title

A Randomized, Double-blinded, Placebo-controlled Trial to Evaluate Chinese Herbal Medicines, Multivitamins and Amino Acid-containing Supplements on Mood and Sleep Quality

Overview

This is a pilot, single-site clinical trial that will follow a randomized, double-blinded, parallel-group, placebo-controlled design. A total of 60 participants aged 18-65 will be recruited for a 12-week intervention, followed by a 4-week observational phase and a post-intervention visit at week 16. Participants will attend five scheduled visits at 4-week intervals (baseline, weeks 4, 8, 12, and 16) at the Specialist Clinical Centre for Teaching and Research, School of Chinese Medicine, the University of Hong Kong (HKUSCM). At each visit, assessments will include psychological attributes and sleep quality. Participants will be randomly allocated to one of 2 groups (n=30 per group): the intervention group, which will receive VCMBF and VCDSF, and the control group, which will receive a placebo matched for appearance, smell, and taste. Written informed consent will be obtained from each participant prior to the commencement of the study. The primary outcome will be overall mental health, accessed by the Depression, Anxiety and Stress Scale - 21 items (DASS-21). Secondary outcomes will include anxiety status, measured by the Chinese version of the Beck Anxiety Inventory (BAI-C); depression status, measured by the Chinese version of the Beck Depression Inventory-II (C-BDI-II); stress levels, measured by the Perceived Stress Scale (PSS); psychological well-being, measured by the General Health Questionnaire-28 (GHQ-28); quality of life, assessed using the WHOQOL-BREF (Hong Kong version); and sleep quality, assessed using the Pittsburgh Sleep Quality Index (PSQI), the Mi wristband as an objective measure, and the Consensus Sleep Diary (CSD) for cross-validation. Tongue and pulse characteristics will also be recorded for qualitative analysis. Safety profiles of VCMBF and VCDSF will be evaluated throughout the study. Assessments will occur every four weeks until week 16, with tongue and pulse characteristics recorded at baseline, week 12, and week 16. A generalized linear mixed-effect model will be applied to compare outcomes over time in the 2 groups.

Detailed description

Mental health issues and sleep disorders have surged globally, especially after COVID-19. In a study analysing over 13 countries throughout the world, rates of anxiety, depression, and insomnia are 25.6%, 23.1%, and 17.4%, respectively. In Hong Kong, 19% suffer from depression, and 14% have anxiety. More generalized symptoms of psychological distress and sleep disturbance are at even higher levels. The overall prevalences for stress, anxiety symptoms, and depressive symptoms are 21.9%, 20.7%, and 17.4%, respectively, in Hong Kong.

Psychological distress is a subclinical state of emotional suffering encompassing anxiety symptoms, depressive symptoms, stress, and functional impairment. Though highly prevalent in the general population, these subtle, milder-than-clinical syndrome manifestations are often unrecognized and untreated, affecting individuals' mental well-being and quality of life significantly and, in time, adding to healthcare costs. Identification of potential protective factors against psychological distress is therefore important.

Sleep and mental well-being are closely related. Somatic symptoms such as sleep disturbance, fatigue, and headache often accompany psychological distress. Sleep, on the other hand, is critical in maintaining physical and psychological well-being, including emotional regulation. Insufficient and poor sleep contributes to higher levels of negative mood and prolonged sleep impairment is associated with depression. Thus, sleep and psychological distress share a bidirectional relationship. Poor sleep can increase psychological distress, while psychological distress can cause and/or worsen sleep issues.

Sleep disturbance and psychological distress, being closely associated, should therefore be considered holistically. Individuals with suboptimal mental well-being states and sleep quality below the threshold for clinical diagnosis often lack options for effective intervention. There is still an unmet need for safe and accessible aids for them, and identification of safe and accessible alternative interventions that improve mood and sleep is greatly desired.

The use of Chinese medicine, vitamins, herbs and other natural compounds that offer health-promoting properties has gained increased attention in recent years, in particular aiding mood, sleep, and psychological symptoms. A vast number of studies have suggested the benefits of Chinese medicines, vitamins, and amino acid supplementary products in improving symptoms of anxiety, depression, and sleep quality. For instance, vitamin B12 deficiency is found to be associated with a higher incidence of depressive mood. L-theanine is found to exert positive effects on relaxation, sleep quality, and mood. It is possible that Chinese medicines, vitamins, and amino acids together can bring about beneficial synergistic effects in improving mood and sleep quality.

Vita Calm Mood Booster Formula (VCMBF) and Vita Calm Deep Sleep Formula (VCDSF) are two health products that are formulated by combining Chinese medicines, multiple vitamins and amino acids. Chinese herbal medicines of VCMBF and VCDSF are formulated adhering to traditional Chinese medicine theory, aligning with concepts of "compatibility of traditional Chinese Medicine" and following the basic Chinese medicine formula structure of "Jun-Chen-Zuo-Shi". VCMBF and VCDSF contain a comprehensive range of micronutrients, including Chinese herbal medicines, vitamins, and amino acids at doses predicted to be sufficient to elicit a response and not likely to elicit adverse effects. The two products are thought to tranquilize anxiety and nervousness, relieve sadness and depression, and improve sleeplessness. Our preliminary animal studies have suggested that Chinese medicines of VCMBF noticeably reduced depression-like behavior in animal models, probably via the modulation of monoamine oxidase (MAO), without inducing herb-drug interaction or hypertension. Chinese medicines of VCDSF rapidly induced sleep in animals and reduced anxiety, and their efficacy was comparable to that of benzodiazepines. A pilot clinical observation revealed that Chinese medicine preparation of VCDSF could improve multiple sleep variables recorded by Actiwatch and diary. Given that psychological distress and sleep disturbance often co-exist in real-life contexts, results of our preliminary studies have encouraged us to further conduct a randomized controlled trial to explore effects and examine the safety of the two investigational products, VCMBF and VCDSF, when used together, on mental well-being and sleep disturbance in adults.

Given the complexities of brain function and comorbidity of psychological issues in real-world contexts, a broad-spectrum, micronutrient approach is suggested to be more effective in contributing to mental health. Emerging evidence also reviewed beneficial outcomes of broad-spectrum micronutrient supplementation on mental health. While many randomized controlled trials have been conducted on multivitamins and nutraceutical formulations, there is a paucity of quality data on assessing the effects and safety of the combined use of Chinese herbal medicines, vitamins and amino acid supplements. Although the mechanism behind synergistic pathways between Chinese medicine, vitamins and amino acids is not addressed in this study due to time and resource limitations, the novelty of the study lies in formally testing the effects and safety of the two multivitamins, amino acids, and herb-containing supplements, VCMBF and VCDSF, when used together, on mental well-being and sleep quality, which is closer to real-life circumstances.

Interventions

• Dietary supplement Vita Calm Mood Booster Formula (VCMBF)
  Vita Calm Mood Booster Formula (VCMBF) Capsule, 2 capsules in the morning
• Dietary supplement Vita Calm Deep Sleep Formula (VCDSF)
  Vita Calm Deep Sleep Formula (VCDSF) Capsule, 2 capsules in the evening
• Dietary supplement Placebo
  Placebo Capsule, 4 capsules in the morning and evening respectively

Primary outcome measures

• Change in the Depression, Anxiety and Stress Scale-21 items score [Time frame: Baseline, Week 4, Week 8, Week 12, Week 16]

Secondary outcome measures (7)

• Change in the Beck Anxiety Inventory score [Time frame: Baseline, Week 4, Week 8, Week 12, Week 16]
• Change in the Beck Depression Inventory-II score [Time frame: Baseline, Week 4, Week 8, Week 12, Week 16]
• Change in the Perceived Stress Scale score [Time frame: Baseline, Week 4, Week 8, Week 12, Week 16]
• Change in the General Health Questionnaire-28 score [Time frame: Baseline, Week 4, Week 8, Week 12, Week 16]
• Change in the World Health Organization Quality of Life-Brief (HK version) score [Time frame: Baseline, Week 4, Week 8, Week 12, Week 16]
• Change in the Pittsburgh Sleep Quality Index score [Time frame: Baseline, Week 4, Week 8, Week 12, Week 16]
• Change in the sleep-wake patterns, sleep duration, and sleep stages [Time frame: Baseline, Week 4, Week 8, Week 12, Week 16]

Eligibility criteria

Inclusion criteria

Participants will be eligible for this study if they:

• are aged 18-65 years;
• have basic Chinese and/or English reading comprehension and expression abilities, and can complete the questionnaire survey independently; and
• are willing and capable of providing signed informed consent; understand and are willing to comply with all study procedures, requirements, and restrictions as listed in the trial protocol and informed consent form; and complete testing and follow-up.

Exclusion criteria

Participants will be excluded if they:

• have unstable systemic medical conditions and/or surgical history that may limit their participation in the study (e.g., severe organ failure, malignancy, neurological conditions, significant cognitive impairment, history of head trauma or surgery, or kidney, liver, or gastrointestinal conditions that might impair food metabolism);
• have a current or past history of an anxiety disorder, major depressive disorder, schizophrenia, bipolar disorder, insomnia, or any other psychiatric illnesses according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5);
• present suicidal ideation (a score of ≥3 for all questionnaires of the Columbia-Suicide Severity Rating Scale (C-SSRS);
• have recent involvement in psychotherapy (e.g., cognitive behavioral therapy, interpersonal psychotherapy, psychodynamic psychotherapy, etc.) and/or behavioral interventions 4 weeks prior to and throughout the study; and/or use of psychiatric medications (e.g., anxiolytic medications, antidepressant medications, etc.) or medications with central nervous system activation (e.g., anticholinergic drugs, acetylcholinesterase inhibitors, etc.) 12 weeks prior to and throughout the study;
• have alcohol abuse (defined as ≥2 drinks per day) or substance abuse;
• are pregnant, in lactation, or intend to conceive during the six months preceding the beginning of the trial;
• are unwilling to abstain from concomitant unnecessary prescription or over-the-counter medications, herbal extracts, vitamins, dietary supplements, illicit or recreational drugs, or vaccines (except oral contraceptive pills) at least 4 weeks prior to and throughout the study, which might interfere with study outcomes;
• have a history of adverse reactions or known allergies to ingredients in the investigational products;
• are unable to ingest pills, or
• are currently participating in or have participated in a program, treatment plan, or research study involving oral administration of investigational product(s) and/or diet, lifestyle modification 4 weeks prior to and throughout the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Supportive care

Study locations

Hong Kong · 1 center

• The University of Hong Kong — Hong Kong

Publications

• Morin CM, Bjorvatn B, Chung F, Holzinger B, Partinen M, Penzel T, Ivers H, Wing YK, Chan NY, Merikanto I, Mota-Rolim S, Macedo T, De Gennaro L, Leger D, Dauvilliers Y, Plazzi G, Nadorff MR, Bolstad CJ, Sieminski M, Benedict C, Cedernaes J, Inoue Y, Han F, Espie CA. Insomnia, anxiety, and depression during the COVID-19 pandemic: an international collaborative study. Sleep Med. 2021 Nov;87:38-45. do PMID 34508986
• Choi EPH, Hui BPH, Wan EYF. Depression and Anxiety in Hong Kong during COVID-19. Int J Environ Res Public Health. 2020 May 25;17(10):3740. doi: 10.3390/ijerph17103740. PMID 32466251
• Sarris J, Ravindran A, Yatham LN, Marx W, Rucklidge JJ, McIntyre RS, Akhondzadeh S, Benedetti F, Caneo C, Cramer H, Cribb L, de Manincor M, Dean O, Deslandes AC, Freeman MP, Gangadhar B, Harvey BH, Kasper S, Lake J, Lopresti A, Lu L, Metri NJ, Mischoulon D, Ng CH, Nishi D, Rahimi R, Seedat S, Sinclair J, Su KP, Zhang ZJ, Berk M. Clinician guidelines for the treatment of psychiatric disorders with PMID 35311615
• Sarris J, Marx W, Ashton MM, Ng CH, Galvao-Coelho N, Ayati Z, Zhang ZJ, Kasper S, Ravindran A, Harvey BH, Lopresti A, Mischoulon D, Amsterdam J, Yatham LN, Berk M. Plant-based Medicines (Phytoceuticals) in the Treatment of Psychiatric Disorders: A Meta-review of Meta-analyses of Randomized Controlled Trials: Les medicaments a base de plantes (phytoceutiques) dans le traitement des troubles psychia PMID 33596697

Identifiers

NCT: NCT06579183 · UW 24-183

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗