A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Tolerability of Product Formulations Containing Mitragynine and Their Relative Effects on Exercise-induced Muscle Soreness in Healthy Adult Participants.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Safety and Tolerability After 28 Days of Use (Vitals)
研究概览
简要总结
This Phase II randomized, double-blind, placebo-controlled study will evaluate the safety, tolerability, and physical dependence potential of mitragynine-containing formulations after 28 days of use and assess their effects on exercise-induced muscle soreness in healthy adults. One hundred participants will be randomized in a 1:1:1:1 ratio to SpecioTea 20 mg, SpecioTea 40 mg, MitraPlex 20 mg, or placebo. Participants will complete an exercise challenge to induce delayed-onset muscle soreness (DOMS), undergo efficacy assessments at 24 and 48 hours post-exercise, and continue daily dosing for approximately 28 days followed by withdrawal and safety assessments.
详细描述
This Phase II study is a prospective, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety, tolerability, and potential physical dependence associated with two mitragynine-containing formulations (SpecioTea and MitraPlex), while also assessing their efficacy in reducing exercise-induced muscle soreness in healthy adults. Participants will be randomized in a 1:1:1:1 ratio to receive SpecioTea 20 mg, SpecioTea 40 mg, MitraPlex 20 mg, or placebo. The study will enroll approximately 100 healthy adults aged 18 to 55 years who are naïve to kratom use or occasional kratom users and who demonstrate delayed-onset muscle soreness (DOMS) following a screening exercise challenge. Randomization will be stratified by sex.
The study duration for each participant will be approximately 11.5 weeks and will consist of a screening period, an acute efficacy phase, a 28-day supplementation period, and post-treatment follow-up assessments. During screening, participants will complete an exercise challenge designed to induce DOMS. Forty-eight hours later, participants will complete a Visual Analogue Scale (VAS) assessment remotely to confirm the presence of muscle soreness and eligibility for enrollment. Eligible participants will return for the baseline visit at least 27 days after the screening exercise challenge.
At baseline, participants will undergo efficacy and safety assessments, including vital signs, laboratory testing, muscle soreness assessment, strength assessment, range of motion measurements, and evaluations using the Subjective Opiate Withdrawal Scale (SOWS) and Clinical Opiate Withdrawal Scale (COWS). Participants will then receive their assigned study intervention and consume the first dose in clinic. Between 45 and 90 minutes after dosing, participants will complete a standardized exercise challenge intended to induce muscle soreness. Biomarkers of muscle damage, including creatine kinase, lactate dehydrogenase, myoglobin, and creatinine, will be measured before and after exercise. Participants will return approximately 24 and 48 hours after the exercise challenge for additional assessments of muscle soreness, muscle strength, range of motion, and biomarkers of muscle damage.
Following completion of the acute exercise phase, participants will begin once-daily at-home dosing for 28 ± 2 days. Participants assigned to active treatment will receive either SpecioTea or MitraPlex capsules providing 20 mg or 40 mg of mitragynine per day, depending on randomization group. Participants assigned to placebo will receive matching placebo capsules. All participants will consume four capsules daily, and study products will be visually identical to maintain blinding.
The primary objective is to evaluate safety and tolerability after 28 days of continued use. Safety assessments include adverse event monitoring, vital signs, body weight, body mass index, hematology and clinical chemistry laboratory evaluations, and assessments of potential withdrawal symptoms using the SOWS and COWS instruments. Safety laboratory assessments include hematology parameters and clinical chemistry measures such as liver function tests, kidney function markers, electrolytes, glucose, and protein measurements.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males and females who are 18 to 55 years of age (inclusive).
- •In good general health as deemed by the investigator and are able to consume the study product.
- •Have a BMI between 18.0 to 34.9 kg/m2 (inclusive).
- •Naïve to kratom use or occasional kratom use (i.e., have not used kratom more than once within 28 days prior to baseline [Visit 2]).
- •Non-smokers (including nicotine vaping) and have not used nicotine-containing products (patches, gums, etc.) for > 3 months prior to baseline (Visit Note: Non-smoker is defined as someone who does not habitually/regularly use products containing nicotine.
- •Appropriate for exercise as determined by the PAR-Q at screening (Visit 1A).
- •Demonstrate DOMS 48 h post-exercise by having a VAS ≥ 40 mm after completion of the exercise challenge at Visit 1A.
- •Agree to follow the restrictions on concomitant treatments.
- •Agree to follow the restrictions on lifestyle (especially regarding physical activity).
- •Agree to use acceptable contraceptive methods.
- •Have suitable veins for repeated venipuncture as deemed by the investigator.
- •Have maintained consistent dietary habits (including medication and supplement intake), exercise and lifestyle habits for the last 3 months before screening (Visit 1A) and agree to maintain them throughout the study (unless required per the restrictions).
- •Willing and able to agree to the requirements of this study, be willing to give voluntary consent, be able to understand and read the questionnaires, and carry out all study-related procedures.
排除标准
- •Individuals who are lactating, planning to become pregnant during the study, or pregnancy as confirmed by a positive urine pregnancy test at screening Visit 1A or Visit
- •Have a positive drug screen for any of the compounds listed as confirmed at screening Visit 1A or Visit
- •Have a known sensitivity, intolerability, or allergy to any of the study products or their excipients, or the rescue medication, NARCAN® (naloxone).
- •Current COVID-19 infections, or currently have the post COVID-19 condition as defined by World Health Organization (WHO) (i.e., individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis).
- •Have exercised regularly (generally > 150 cumulative minutes per week) for 6 months prior to screening (Visit 1A) and/or Visit
- •Have engaged in regular lower extremity fitness activities (e.g., running, cycling, soccer or hockey) for more than two times per week for ≥ 2 consecutive weeks in the past 6 months prior to screening (Visit 1A) and/or Visit
- •Had lower body surgery (e.g., hips, knees, ankles, etc.) within 6 months prior to screening (Visit 1A) and/or planned lower body surgery during the study.
- •History of any lower body injury [e.g., partial anterior cruciate ligament (ACL) tear, broken or fractured bone, major sprain] within 6 months prior to screening (Visit 1A) and/or during the study.
- •Have Type I/Type II diabetes or thyroid disease.
- •Have uncontrolled or controlled high blood pressure (≥140 systolic or ≥90 diastolic mmHg) at screening.
- •Have medical condition(s) known to interfere with absorption, distribution, metabolism, or excretion of the study product (e.g., Crohn's disease, short bowel, acute or chronic pancreatitis, or pancreatic insufficiency).
- •Have a history of heart/cardiovascular disease, immune disorders and/or immunocompromised (i.e., HIV/AIDS).
- •Have active asthma or have experienced an asthma attack in the last 5 years.
- •Have a history of neurological disorders such as epilepsy.
- •Have hepatic or renal dysfunction as evidenced by ALT and/or AST being ≥ 2 times the upper limit of normal (ULN), serum creatinine or urea value ≥ 1.5 times the ULN, or other clinically significant abnormal clinical laboratory value per investigator discretion.
- •Have a history of cancer (except localized skin cancer without metastases or in situ cervical cancer), unless recovery occurred more than 5 years before the screening visit.
- •Are receiving treatments for or have been hospitalized in the last 12 months for psychiatric disorders (e.g., depression, bipolar disorder, schizophrenia, etc.).
- •Have known genetic polymorphisms of CYP450, CYP3A4, CYP2D6, and/or CYP1A2 enzymes.
- •Reports a clinically significant illness during the 28 days before the first dose of study product.
- •Major surgery in 3 months prior to screening or planned major surgery during the study.
- •Reports a significant blood loss or blood donation totaling between 101 mL to 449 mL of blood within 30 days prior to Visit 2 or a blood donation of more than 450 mL within 56 days prior to Visit
- •Reports donating plasma (e.g., plasmapheresis) within 15 days prior to Visit
- •Have a history of alcohol or substance abuse in the 12 months prior to Visit 1A (including having been hospitalized for such in an in-patient or out-patient intervention program) or use that to the opinion of the investigator may be of a concern for the study.
- •Currently consumes more than 2 standard alcoholic beverages per day on average for 4 weeks prior to Visit 1A. A standard alcoholic beverage is defined as 12 ounces of beer, 5 ounces of wine or 1.5 ounces of liquor.
- •Evidence of addictive tendency as indicated by an LDQ score ≥ 21 at Visit 1A.
- •Current enrolment or past participation in another study with any product(s) with at least one active ingredient within 28 days before Visit 1A or longer, if the previous test product is deemed by the investigator to have lasting effects that might influence the eligibility criteria or outcomes of current study.
- •Living in the same household as another currently/previously enrolled participant in the present study.
- •Any other medical condition/situation or use of medications/supplements/therapies that, in the opinion of the investigator, may adversely affect the participant's ability to participate in the study or its measures or pose a significant risk to the participant.
研究组 & 干预措施
SpecioTea 20 mg
Participants receive 4 capsules daily containing a total of 20 mg mitragynine (2 active capsules plus 2 placebo capsules).
干预措施: SpecioTea (Dietary Supplement)
SpecioTea 40 mg
Participants receive 4 active capsules daily containing a total of 40 mg mitragynine.
干预措施: SpecioTea (Dietary Supplement)
MitraPlex 20 mg
Participants receive 4 active capsules daily containing a total of 20 mg mitragynine.
干预措施: MitraPlex (Dietary Supplement)
Placebo
Participants receive 4 placebo capsules daily.
干预措施: Placebo (Other)
结局指标
主要结局
Safety and Tolerability After 28 Days of Use (Vitals)
时间窗: Baseline through Visit 7 (approximately 45 days) with primary safety assessment after 28 ± 2 days of dosing.
Heart Rate (bpm)
To assess the effect of each TP intervention on changes in creatinine compared to each other and to a placebo
时间窗: Change from baseline to 1 hour, 24 hours, and 48 hours post-exercise
Change in concentration of creatinine
To assess the effect of each TP intervention on changes in myoglobin compared to each other and to a placebo
时间窗: Change from baseline to 1 hour, 24 hours, and 48 hours post-exercise
Change in concentration of myoglobin
To assess the effect of each TP intervention on changes in lactose dehydrogenase (LDH) compared to each other and to a placebo
时间窗: Change from baseline to 1 hour, 24 hours, and 48 hours post-exercise
Change in concentration of LDH
To assess the effect of each TP intervention on changes in CK compared to each other and to a placebo
时间窗: Change from baseline to 1 hour, 24 hours, and 48 hours post-exercise
Change in concentration of creatine kinase (CK)
To assess the effect of each TP intervention on muscle strength after intense exercise compared to each other and to a placebo
时间窗: Change from baseline to 24 hours and 48 hours post-exercise
Change in the maximum weight moved
To assess the effect of each TP intervention on reducing joint stiffness after intense exercise compared to each other and to a placebo
时间窗: Change from baseline to 24 hours and 48 hours post-exercise
Change in the magnitude of joint range of motion (degrees)
To assess the efficacy of each TP intervention on reducing exercise-induced muscle soreness at 24 h and 48 h post-exercise compared to each other and to a placebo
时间窗: Change from baseline to 24 hours and to 48 hours post-exercise
Change in Visual Analog Scale score. Participants will draw a vertical line on 100 mm scale that represents the current intensity of their pain where left end of the scale is representative of "no soreness at all" and the right end of the scale is representative of "extreme soreness". The intensity of pain will be considered to be the distance (in mm) of the participant's mark from the left-hand side of the scale.
Safety and Tolerability After 28 Days of Use (Anthropometrics)
时间窗: Baseline through Visit 7 (approximately 45 days) with primary safety assessment after 28 ± 2 days of dosing.
Assessment of Body weight (kg)
Safety and Tolerability After 28 Days of Use (Laboratory Blood Tests)
时间窗: Baseline through Visit 7 (approximately 45 days) with primary safety assessment after 28 ± 2 days of dosing.
Blood samples will be collected to assess hematology parameters (hemoglobin, hematocrit, red blood cell \[RBC\], red blood cell distribution width \[RDW\], RBC indices \[mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), MCH concentration (MCHC)\], white blood cells \[WBC\] with differential \[abs\], platelet count, mean platelet volume \[MPV\]).
Safety and Tolerability After 28 Days of Use (Adverse Events)
时间窗: Baseline through Visit 7 (approximately 45 days) with primary safety assessment after 28 ± 2 days of dosing.
Reports of AEs
Safety and Tolerability After 28 Days of Use (SOWS)
时间窗: Baseline through Visit 7 (approximately 45 days) with primary safety assessment after 28 ± 2 days of dosing.
Changes in Subjective Opiate Withdrawal Scale (SOWS) scores for grading opioid withdrawal symptoms. A SOWS total score of 1-10 is considered mild, 11-20 moderate and 21-30 severe. On both scales, greater scores correspond to increased perception of any of the symptoms.
Safety and Tolerability After 28 Days of Use (COWS)
时间窗: Baseline through Visit 7 (approximately 45 days) with primary safety assessment after 28 ± 2 days of dosing.
Changes in Clinical Opiate Withdrawal Scale (COWS) scores which is the summed score used to determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids (score of below 5 = no withdrawal; 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal).
次要结局
未报告次要终点