Clinical trial NCT05994794: Role of a Dietary Supplement in Lowering SAH in Healthy Adults With Elevated Plasma SAH and Normal Homocysteine Levels
Official title: A Randomized, Single-Blind, Placebo-Controlled Trial for the Role of a Dietary Supplement in Lowering S-Adenosylhomocysteine (SAH) in Healthy Adults With Elevated Plasma SAH and Normal Homocysteine Levels and Identification of Participants With Elevated Plasma SAH in the General Population Using the MethylQ Score
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Elevated S-adenosylhomocysteine
Keywords: Methylation
Alpha-GPC
Creatine
Ashwagandha
Lead sponsor: Standard Process Inc.
Sponsor class: INDUSTRY
Collaborators: name: Nutrasource Pharmaceutical and Nutraceutical Services, Inc.
First posted: 2023-08-16
Enrollment: 40
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: S-adenosylhomocysteine (SAH) is the end-product of methylation reactions in the body and the precursor to homocysteine. Elevated SAH in the blood is a reflection of the dysregulation of what is known as the S-adenosylmethionine (SAM) cycle and has been associated with poor health outcomes. The SAM cycle is a series of reversible reactions necessary for the regulation of many processes in the body.

The goal of this clinical trial is to assess the ability of a dietary supplement to support healthy plasma SAH levels in individuals with high plasma SAH.

Participants in the study will attend a total of 4 clinic visits and consume study product daily for 12 weeks.

Detailed description: Methionine, a dietary amino acid commonly found in meats, is processed by the body and yields the by-product S-adenosylhomocysteine (SAH), which then undergoes condensation with ATP to produce S-adenosylmethionine (SAM). SAM is the main methyl donor in many of the reactions that occur in the cell. These methyl reactions are well-known epigenetic mechanisms involved in DNA gene expression. When SAM donates its methyl group in a reaction, it becomes SAH which participates in a reversible reaction with homocysteine. Homocysteine is then removed through re-methylation to methionine using folate and vitamin B12. This decrease in homocysteine levels prevents the over-production of SAH, which can disrupt the methyl reactions throughout the body. Dysregulation of this pathway leads to elevated levels of SAH, which have been associated with various disease states. Therefore, an intervention which can lower SAH may ameliorate the outcomes associated with its elevation. This trial will evaluate the efficacy of a dietary supplement to lower SAH in individuals with elevated SAH and normal homocysteine. In addition, this study aims to explore the correlation between the MethylQ score (derived from 3 questionnaires) and measures of SAH level and the SAM:SAH ratio.

The test product contains alpha-GPC, creatine, and ashwagandha. Individually, these ingredients have been shown to improve levels of either SAH or homocysteine in clinical trials.

Participants will be assigned to either the test product or placebo at a 5:3 and consume study product orally for 12 weeks. Assessment measures will include methylation biomarkers, free cortisol index, mood states and MethylQ score in individuals with elevated SAH levels (≥ 20 nmol/L) and normal homocysteine (≤ 13 µmol/L).

The study will include a screening visit followed by a screening period lasting up to 90 days in duration with a remote check-in via phone call occurring between Day -40 and Day -30 (inclusive) for participants screened more than 30 days prior to the baseline visit on (Visit 2). Following the screening period, participants will attend a baseline visit on Day 1, an interim visit on Day 43 ± 3, and an end of study visit on the day after the 12-week (± 3 days) study product use (Day 85 ± 3). The study will include a total of 4 in-person visit days: a screening visit (Visit 1), a baseline visit (Visit 2), an interim visit (Visit 3), and an EOS visit (Visit 4).

Eligibility criteria: Inclusion Criteria:

1. Healthy adults who are 30 to 75 years of age (inclusive).
2. Have a BMI between 18.5 to 34.9 kg/m\^2 (inclusive).
3. In good general health (no uncontrolled diseases or conditions) as deemed by the investigator and is able to consume the study product.
4. Have elevated plasma SAH levels of ≥ 20 nmol/L and normal plasma homocysteine levels of ≤ 13 µmol/L at the screening visit (Visit 1).
5. Individuals with childbearing potential must agree to practice an acceptable form of birth control for a certain timeframe prior to the first dose of study product and throughout the study, including:

   1. use for at least 3 months prior to the first dose of study product: hormonal contraceptives including oral contraceptives, hormone birth control patch (e.g., Ortho Evra), vaginal contraceptive ring (e.g., NuvaRing), injectable contraceptives (e.g., Depo-Provera, Lunelle), or hormone implant (e.g., Norplant System), or intrauterine devices (e.g., Mirena); or
   2. use for at least 1 month prior to the first dose of study product: double-barrier method, non-hormonal intrauterine devices (i.e., copper), or complete abstinence from sexual intercourse that may result in pregnancy; or
   3. vasectomy of partner at least 6 months prior to the first dose of study product.

   Individuals with the potential to impregnate others must agree to use condoms or other acceptable methods to prevent pregnancy throughout the study. Complete abstinence from sexual intercourse that may result in pregnancy is also acceptable.
6. Agree to comply with concomitant treatment restrictions, permitted time frames and/or conditions listed in Study Protocol (No. S01-21-01-T0023) Section 6.5 (Concomitant Treatments).
7. Have maintained stable dietary habits (including supplement intake), exercise habits and lifestyle for the last 3 months prior to screening and agree to maintain dietary and exercise habits and lifestyle throughout the study.
8. Willing and able to agree to the requirements and restrictions of this study, be willing to give voluntary consent, be able to understand and read the questionnaires, and carry out all study-related procedures.

Exclusion Criteria:

1. Individuals who are lactating, pregnant or planning to become pregnant during the study as confirmed at the baseline visit (Visit 2).
2. Have a known sensitivity, intolerability, or allergy to any of the study products or their excipients.
3. Currently has COVID-19 or tests positive for COVID-19 within 28 days prior to baseline visit.
4. Currently has any post Covid-19 condition(s) as defined by World Health Organization (WHO) (i.e., individuals with a history of a probable or confirmed SARS-CoV-2 infection, usually three months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis).
5. Have a history of heart disease/cardiovascular disease, uncontrolled hypertension (140/90 or greater mmHg), kidney dysfunction or disease (dialysis or renal failure), hepatic impairment or disease, or Type I or Type II diabetes.
6. Have a history of thyroid disease, major affective disorder, psychiatric disorder (e.g., bipolar disorder) that required hospitalization in the prior year, autoimmune diseases (e.g., multiple sclerosis, Parkinson's, systemic lupus erythematosus, rheumatoid arthritis, etc.), or immune disorder (i.e., HIV/AIDS).
7. Have an abnormality or obstruction of the gastrointestinal tract precluding swallowing (e.g. dysphagia) and digestion (e.g., known intestinal malabsorption, celiac disease, inflammatory bowel disease, chronic pancreatitis, steatorrhea).
8. Have an active malignant disease, except basal or squamous cell skin carcinoma or carcinoma in situ of the uterine cervix.
9. Major surgery in 3 months prior to the screening visit (Visit 1) or planned major surgery during the course of the study.
10. History of alcohol or substance abuse in the 12 months prior to screening (including having been hospitalized for such in an in-patient or out-patient intervention program).
11. Receipt or use of test product(s) in another research study within 28 days prior to baseline 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.
12. Any other active or unstable medical conditions or use of medications/supplements/ therapies that, in the opinion of the investigator, may adversely affect the participant's ability to complete the study or its measures or pose a significant risk to the participant.

Primary outcomes:
measure: To determine the effect of the Test Product (TP) compared to placebo on plasma S-adenosylmethionine (SAM) concentration.
timeFrame: 12 weeks
measure: To determine the effect of the TP compared to placebo on plasma S-adenosylhomocysteine (SAH) concentration.
timeFrame: 12 weeks
measure: To determine the effect of the TP compared to placebo on plasma homocysteine concentration.
timeFrame: 12 weeks
measure: To determine the effect of the TP compared to placebo on plasma cystathionine concentration.
timeFrame: 12 weeks
measure: To determine the effect of the TP compared to placebo on plasma cysteine concentration.
timeFrame: 12 weeks
measure: To determine the effect of the TP compared to placebo on plasma methionine concentration.
timeFrame: 12 weeks
Secondary outcomes:
measure: To determine the effect of the TP compared to placebo on plasma SAM concentration.
timeFrame: 6 weeks
measure: To determine the effect of the TP compared to placebo on plasma SAH concentration.
timeFrame: 6 weeks
measure: To determine the effect of the TP compared to placebo on plasma homocysteine concentration.
timeFrame: 6 weeks
measure: To determine the effect of the TP compared to placebo on plasma cystathionine concentration.
timeFrame: 6 weeks
measure: To determine the effect of the TP compared to placebo on plasma methionine concentration.
timeFrame: 6 weeks
measure: To determine the effect of the TP compared to placebo on plasma cysteine concentration.
timeFrame: 6 weeks
measure: To determine the effect of the TP compared to placebo on overall mood state.
timeFrame: 12 weeks
measure: To determine the effect of the TP compared to placebo on anger-hostility.
timeFrame: 12 weeks
measure: To determine the effect of the TP compared to placebo on vigor-activity.
timeFrame: 12 weeks
measure: To determine the effect of the TP compared to placebo on confusion-bewilderment.
timeFrame: 12 weeks
measure: To determine the effect of the TP compared to placebo on depression-dejection.
timeFrame: 12 weeks
measure: To determine the effect of the TP compared to placebo on tension-anxiety.
timeFrame: 12 weeks
measure: To determine the effect of the TP compared to placebo on friendliness.
timeFrame: 12 weeks
measure: To determine the effect of the TP compared to placebo on fatigue-inertia.
timeFrame: 12 weeks
measure: To determine the effect of the TP compared to placebo on free cortisol index.
timeFrame: 12 weeks
measure: To determine the effect of the TP compared to placebo on the MethylQ score.
timeFrame: 12 weeks
Other outcomes:
measure: MethylQ score and Plasma SAH Correlation
timeFrame: Screening, Baseline and Week 12
measure: MethylQ score and SAM/SAH Ratio Correlation
timeFrame: Screening, Baseline and Week 12
measure: Post-dose change in Plasma SAH and MethylQ score Correlation
timeFrame: 12 weeks
measure: Post-dose change in SAM/SAH Ratio and MethylQ score Correlation
timeFrame: 12 weeks
measure: Heart rate
timeFrame: 12 weeks
measure: Blood pressure
timeFrame: 12 weeks
measure: Body weight
timeFrame: 12 weeks
measure: Body mass index
timeFrame: 12 weeks
measure: Whole Blood Hemoglobulin
timeFrame: 12 weeks
measure: Whole Blood Hematocrit
timeFrame: 12 weeks
measure: Whole Blood White Blood Cells
timeFrame: 12 weeks
measure: Whole Blood Neutrophils
timeFrame: 12 weeks
measure: Whole Blood Basophils
timeFrame: 12 weeks
measure: Whole Blood Eosinophils
timeFrame: 12 weeks
measure: Whole Blood Monocytes
timeFrame: 12 weeks
measure: Whole Blood Lymphocytes
timeFrame: 12 weeks
measure: Whole Blood Red Blood Cell Count
timeFrame: 12 weeks
measure: Whole Blood Red blood cell distribution width
timeFrame: 12 weeks
measure: Whole Blood Mean Corpuscular Volume
timeFrame: 12 weeks
measure: Whole Blood Mean Corpuscular Hemoglobin
timeFrame: 12 weeks
measure: Whole Blood Mean Corpuscular Hemoglobin Concentration (MCHC)
timeFrame: 12 weeks
measure: Whole Blood Platelet count
timeFrame: 12 weeks
measure: Whole Blood Mean platelet volume (MPV)
timeFrame: 12 weeks
measure: Serum Sodium
timeFrame: 12 weeks
measure: Serum Potassium
timeFrame: 12 weeks
measure: Serum Chloride
timeFrame: 12 weeks
measure: Serum Urea
timeFrame: 12 weeks
measure: Serum Creatinine
timeFrame: 12 weeks
measure: Estimate glomerular filtration rate (eGFR)
timeFrame: 12 weeks
measure: Serum Total Protein
timeFrame: 12 weeks
measure: Serum Albumin
timeFrame: 12 weeks
measure: Serum Globulin
timeFrame: 12 weeks
measure: Serum Total Bilirubin
timeFrame: 12 weeks
measure: Serum Fasting Glucose
timeFrame: 12 weeks
measure: Serum Alkaline phosphatase
timeFrame: 12 weeks
measure: Serum Alanine transaminase
timeFrame: 12 weeks
measure: Serum Aspartate transaminase
timeFrame: 12 weeks
measure: Incidence of adverse events
timeFrame: 12 weeks
Locations:
city: S. Gate
country: United States
facility: Valiance Clinical Research
state: California
Study officials:
affiliation: Nutrition Innovation Center, Standard Process Inc.
name: Bassem F. El-Khodor, PhD
role: PRINCIPAL_INVESTIGATOR
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