ClinicalTrials.gg
Not yet recruitingNCT07836712Updated Sep 23, 2026

Multiple Adjunct Therapies to Improve Immunotherapy Treatment in Patients With Locally Advanced or Metastatic Melanoma or Advanced Hepatocellular Cancer

A Phase 2 interventional study of Biospecimen Collection and Cholecalciferol in Advanced Hepatocellular Carcinoma, Advanced Melanoma and Locally Advanced Melanoma, sponsored by University of Southern California. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-23.

Sponsored by University of Southern California · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
46
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This clinical trial tests the effect of multiple therapies (propranolol, desloratadine, and magnesium and vitamin D supplements) added to primary standard of care immunotherapy (adjunct), as well as adjusting the timing of standard immunotherapy to a morning infusion, in treating patients with melanoma that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started to other places in the body (metastatic) or hepatocellular cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Propranolol is a medication used for high blood pressure. Desloratadine is a type of drug that blocks the action of histamines, which can cause fever, itching, sneezing, a runny nose, and watery eyes. Immunotherapy has been approved for multiple kinds of advanced cancers, including melanoma, kidney cancer, non-small cell lung cancer and hepatocellular (liver) cancer. Research suggests that giving propranolol and desloratadine, along with ensuring adequate levels of magnesium and vitamin D, as well as administering immunotherapy infusions in the morning may shrink or stop the spread of advanced cancers better than immunotherapy alone.

Read the detailed description

PRIMARY OBJECTIVE:

I. Compare levels of biomarkers of immunomodulation, specifically interleukin (IL)-8, interferon gamma (IFN-y), effector T cells (Teff)/regulatory T cell (Treg) ratio, over a 12-week period, in peripheral blood of patients undergoing standard of care PD-1/PD-L1-containing immunotherapy regimens for advanced cancers randomized to Arm A or Arm B.

SECONDARY OBJECTIVE:

I. Evaluate the safety and tolerability of the combination of: magnesium, vitamin D supplements; desloratadine; propranolol in patients undergoing morning infusion of standard of care PD-1/PD-L1-containing immunotherapy regimens in Arm A.

EXPLORATORY OBJECTIVES:

I. Compare additional biomarkers of immunomodulation (including [incl.] cytokines, metabolites, select metal ion levels, flow cytometry, circulating tumor deoxyribonucleic acid [ctDNA]) over a 12-week period, in peripheral blood of patients undergoing standard of care PD-1/PD-L1-containing immunotherapy regimens for advanced cancers randomized to Arm A or Arm B.

II. Compare the preliminary clinical benefit using time to next treatment (TTNT) in patients undergoing standard of care PD-1/PD-L1-containing immunotherapy regimens for advanced cancers randomized to Arm A or Arm B.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive standard of care PD-1/PD-L1-containing immunotherapy infusion, starting before 12 PM, desloratadine orally (PO) once daily (QD), propranolol PO twice daily (BID), magnesium intravenously (IV) if magnesium level is below 1.9, and vitamin D PO QD if vitamin D level is below 30. Additional IV or oral magnesium and vitamin D supplementation may be administered at the investigator's discretion per standard of care. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) and blood sample collection throughout the study.

ARM B: Patients receive standard of care PD-1/PD-L1-containing immunotherapy, starting at standard of care time. Magnesium and vitamin D levels are checked with any supplementation per investigator discretion and institutional practice, without a prespecified goal level. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 3 months.

02

Conditions studied

  • Advanced Hepatocellular Carcinoma
  • Advanced Melanoma
  • Locally Advanced Melanoma
  • Metastatic Melanoma
  • Stage III Hepatocellular Carcinoma AJCC v8
  • Stage IV Hepatocellular Carcinoma AJCC v8
03

In context

Melanoma

3,370 studies on the registry are indexed under Melanoma; 578 are open to participants now.

This study's planned enrollment of 46 is above the median of 40 across 2,649 interventional studies indexed under Melanoma.

Browse Melanoma studies →

Lead sponsor

University of Southern California is the lead sponsor of 791 studies on the registry; 136 are open to participants now.

Of its 70 completed or terminated interventional studies of FDA-regulated products, 32 (46%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • or cytologically confirmed locally advanced or melanoma or advanced hepatocellular cancer (HCC); histologic/cytologic confirmation not required for HCC
  • Eligible and planned to begin therapy with PD1/PDL-1 inhibitors as standard of care therapy, either as monotherapy or in combination with other approved or bevacizumab
  • Age ≥ 18 years
  • (ECOG) performance status 0-2
  • ≥ 1,000/mcl
  • ≥ 8.0 g/dL
  • ≥ 75,000/mcl
  • Total ≤ 1.5 × (ULN) or ≤ 3 × ULN in Gilbert's syndrome
  • (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × ULN for patients without liver metastasis ≤ 5 × ULN for patients with liver metastasis
  • > 30 mL/min per Cockcroft-Gault
  • Females of must agree to sexual abstinence (defined below) or be willing to use a highly effective method of from the start of therapy through 90 days after the completion of therapy.

Non-childbearing potential is defined as:

  • , defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
  • Surgically sterile. Surgical sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.

Acceptable highly effective birth control methods include:

  • Oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
  • Oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation
  • Intrauterine device
  • Intrauterine hormone-releasing system
  • Bilateral tubal occlusion
  • Vasectomized partner (provided that partner is the sole sexual partner of the female of and that the vasectomized partner has received medical assessment of the surgical success)
  • Sexual abstinence. In the context of this study sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse from the start of therapy through 90 days after the completion of therapy

    • Males who have female partners of childbearing potential must agree to use a highly effective method of contraception from the start of therapy through 90 days after the completion of therapy
    • Ability to understand and the willingness to sign a written

Exclusion criteria

Exclusion Criteria:

  • Prior systemic anticancer therapy for locally advanced or disease. Therapy in the or adjuvant setting is allowed if the last dose of neo/adjuvant therapy is at least 6 months prior to first dose of study treatment
  • A known history or disease requiring systemic therapy; or any disease process requiring systemic immunosuppressive therapy (e.g. high-dose defined as ≥ 10 mg prednisone or equivalent per day).

    • Note: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed
  • History of grade ≥ 3 immune-related adverse event(s) associated with prior immunotherapy, unless these events did not require hospitalization, were manageable with medical therapy, and adequately resolved within 14 days
  • Medical requirement for beta blockers or histamine 1 (H1) blockers
  • Has active central nervous system (CNS) metastases and/or any history of

    • Note: Patients with previously treated may participate provided they are radiologically stable (i.e. no evidence of progression for ≥ 4 weeks by repeat imaging performed during study screening), clinically stable, and not requiring steroid treatment within 14 days prior to first dose of study treatment
  • Has received a administered within 28 days of planned treatment start or while participating in the study
  • Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
  • History of or current condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate
  • to the use of beta-blockers, including but not limited to unstable angina pectoris, uncontrolled heart failure (Grade III or IV), hypotension (systolic blood pressure \< 100 mmHg), bradycardia
  • Patients must not be receiving other concomitant biologic therapy, hormonal therapy, chemotherapy, other anti-cancer therapy or any other agents while on this protocol
Terms in these criteria, in plain language(26)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Histologically or cytologically confirmed

The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).

Your pathology report is the document that shows this.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Line of therapy

A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.

“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.

PD-1, PD-L1 and checkpoint inhibitors

PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.

PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Postmenopausal

Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).

Reproductive potential

Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.

Criteria about it usually ask for contraception during the study and for a time after it.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Adjuvant and neoadjuvant

Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Leptomeningeal disease

Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.

Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.

Brain metastases

Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).

Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.

Live vaccines

Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
46 participants (estimated)

Study arms

  • Experimental
    Arm A (Adjunct interventions)

    Patients receive standard of care PD-1/PD-L1-containing immunotherapy infusion, starting before 12 PM, desloratadine PO QD, propranolol PO BID, magnesium IV if magnesium level is below 1.9, and vitamin D PO QD if vitamin D level is below 30. Additional IV or oral magnesium and vitamin D supplementation may be administered at the investigator's discretion per standard of care. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study.

    Procedure: Biospecimen Collection · Dietary Supplement: Cholecalciferol · Procedure: Computed Tomography · Drug: Desloratadine · Other: Immunotherapy · Procedure: Infusion Procedure · Drug: Magnesium Sulfate · Procedure: Magnetic Resonance Imaging · Drug: Propranolol

  • Active comparator
    Arm B (Standard interventions)

    Patients receive standard of care PD-1/PD-L1-containing immunotherapy, starting at standard of care time. Magnesium and vitamin D levels are checked with any supplementation per investigator discretion and institutional practice, without a prespecified goal level. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study.

    Procedure: Biospecimen Collection · Procedure: Computed Tomography · Other: Immunotherapy · Procedure: Infusion Procedure · Procedure: Magnetic Resonance Imaging

Interventions

  • ProcedureBiospecimen Collection

    Undergo blood sample collection

    Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

  • Dietary supplementCholecalciferol

    Given PO

    Also known as: 9,10-Secocholesta-5,7,10(19)-trien-3-ol, Calciol, Delsterol, Vitamin D3

  • ProcedureComputed Tomography

    Undergo CT scan

    Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

  • Given PO

    Also known as: Clarinex, Sch 34117

  • OtherImmunotherapy

    Given standard of care immunotherapy

    Also known as: Immunological, Immunological Therapy, Immunologically Directed Therapy

  • ProcedureInfusion Procedure

    Immunotherapy infusion given prior to 12 PM

    Also known as: Infused, Infusion

  • ProcedureInfusion Procedure

    Infusion given per standard of care timing

    Also known as: Infused, Infusion

  • Given IV

    Also known as: Magnesium SO4, Magnesium Sulfate whiskers, MAGNESIUM SULFATE, UNSPECIFIED FORM

  • ProcedureMagnetic Resonance Imaging

    Undergo MRI

    Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

  • Given PO

    Also known as: 1-[(1-Methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanol

06

What researchers measure

Primary outcomes

  1. Change in interleukin-8 levels

    The estimand for the null hypothesis will be the estimate of the difference in the average characteristics at week 12 stratified by the disease group. The null hypothesis will be tested at the 0.05 level. Tests of the null hypothesis will be conducted using the t-test. Departures from the normal distribution of the estimand will be assessed using the Shapiro-Wilk test.

    Time frame: From baseline to 12 weeks

  2. Change in interferon-gamma levels

    The estimand for the null hypothesis will be the estimate of the difference in the average characteristics at week 12 stratified by the disease group. The null hypothesis will be tested at the 0.05 level. Tests of the null hypothesis will be conducted using the t-test. Departures from the normal distribution of the estimand will be assessed using the Shapiro-Wilk test.

    Time frame: From baseline, up to 12 weeks

  3. Change in effector T cells (Teff)/regulatory T cell (Treg) ratio

    The estimand for the null hypothesis will be the estimate of the difference in the average characteristics at week 12 stratified by the disease group. The null hypothesis will be tested at the 0.05 level. Tests of the null hypothesis will be conducted using the t-test. Departures from the normal distribution of the estimand will be assessed using the Shapiro-Wilk test.

    Time frame: From baseline, up to 12 weeks

Secondary outcomes

  1. Incidence of grade ≥ 3 treatment related adverse events (AEs)

    Will report the frequency of treatment-related AEs, treatment-emergent SAEs during treatment with immunoadjuvant treatment for patients randomized to Arm A and through the first 12 protocol weeks for Arm B. For each evaluable patient, the maximum grade of each Common Terminology Criteria for Adverse Events (CTCAE) version 6 codable toxicity will be determined. For any AE event that occurs in at least one patient at grade 3 or greater, the rate of occurrence will be compared between the two randomized groups using the exact conditional test of proportions.

    Time frame: From baseline, up to 12 weeks

  2. Incidence of immune related AEs

    Will report the frequency of immune related AEs during treatment for patients randomized to Arm A and through the first 12 protocol weeks for Arm B using Common Terminology Criteria for Adverse Events (CTCAE) version 6.

    Time frame: From baseline, up to 12 weeks

  3. Incidence of serious AEs

    Will report the frequency of serious AEs during treatment for patients randomized to Arm A and through the first 12 protocol weeks for Arm B using Common Terminology Criteria for Adverse Events (CTCAE) version 6.

    Time frame: From baseline, up to 12 weeks

07

Study locations

1 site
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California 90033, United States
    • Diana Hanna · Contact323-865-3000
    • Diana Hanna · Principal investigator
08

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Start is estimated for Nov 2026; primary completion for Nov 2027, 12 months later.

Of 277 non-industry phase 2 interventional studies under Melanoma, half reached primary completion within 67 months of starting (the median), counting those still running; a quarter within 41 and three quarters within 94. This study's planned 12 months is below that.

Counting every sponsor, half of 383 studies reached it within 53 months; a quarter within 32 and three quarters within 88.

How these figures are worked out, and which studies are left out of them.

Registered
Sep 17, 2026
First posted
Sep 23, 2026
StartEst.
Nov 1, 2026
Primary completionEst.
Nov 1, 2027
CompletionEst.
Nov 1, 2028
Last update
Sep 23, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 23, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT07836712
Responsible party
Sponsor
First posted
Sep 23, 2026
Start date
Nov 1, 2026 (estimated)
Primary completion
Nov 1, 2027 (estimated)
Completion
Nov 1, 2028 (estimated)
Last update
Sep 23, 2026

Study contacts

Diana Hanna
principal investigator · University of Southern California

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

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Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drugs tested here: Cholecalciferol · Desloratadine · Magnesium Sulfate · Propranolol

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