Cosyntropin Test for Adrenal Fatigue

Recruiting at 1 trial location

Overseen By Noah Bloomgarden, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Montefiore Medical Center

Must be taking: Glucocorticoids

Must not be taking: Estrogens, Barbiturates, Phenytoin, others

Disqualifiers: Liver impairment, Renal impairment, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal cortisol levels for diagnosing adrenal insufficiency, a condition where the body doesn't produce enough cortisol for daily activity. The trial uses cosyntropin (a synthetic form of adrenocorticotropic hormone) and involves three groups: individuals with known adrenal insufficiency, healthy volunteers, and those suspected of having the condition. Participants with a history of adrenal insufficiency or symptoms suggesting it might be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to important research that could enhance diagnostic methods for adrenal insufficiency.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop using certain medications, such as estrogen preparations, medications that affect liver enzymes, and biotin within 72 hours. Healthy volunteers must also stop using glucocorticoids and certain other medications for specific periods before the trial.

What prior data suggests that Cosyntropin is safe for diagnosing adrenal insufficiency?

Research has shown that cosyntropin is generally safe for people and is often used to check for adrenal gland problems. Studies have found that most patients tolerate it well. Side effects are usually mild and might include temporary discomfort or irritation at the injection site.

Cosyntropin is approved for diagnosing adrenal issues, which supports its safety. However, like any medical treatment, a small chance of side effects exists. Discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to provide a clearer understanding of cortisol levels in different populations using Cosyntropin. Current methods for diagnosing adrenal insufficiency rely on measuring cortisol levels, but there is variability in these measurements. This trial seeks to refine these measurements by comparing cortisol responses in healthy individuals, those with known adrenal insufficiency, and those suspected of having the condition. By doing so, researchers hope to enhance the accuracy of adrenal insufficiency diagnoses, which could lead to more precise and effective treatment plans.

What evidence suggests that Cosyntropin might be an effective treatment for adrenal insufficiency?

Research has shown that cosyntropin is highly effective for diagnosing adrenal insufficiency. One study found the cosyntropin test to be 95% accurate in identifying individuals without the condition and correctly detecting primary adrenal insufficiency in 97% of cases. In this trial, participants will be divided into groups: those with known adrenal insufficiency, healthy volunteers, and those suspected of having adrenal insufficiency. The test mimics the hormone ACTH, prompting the body to produce cortisol. This process helps doctors identify different types of adrenal issues, making it a reliable tool for diagnosing low cortisol levels, which are essential for daily life. ^{5 6 7 8 9}

Who Is on the Research Team?

Smita B Abraham, MD

Principal Investigator

Albert Einstein - Montefiore Medical Center, Bronx, New York

Are You a Good Fit for This Trial?

This trial is for adults over 18 who may have adrenal insufficiency, which means their bodies don't make enough cortisol. It's open to those with a suspected or confirmed diagnosis but not currently on certain steroids, opioids, or other excluded medications. Pregnant women and individuals with specific health conditions like severe liver or kidney issues can't participate.

Inclusion Criteria

I am 18 or older and have never been diagnosed with adrenal insufficiency.

I am 18 or older with adrenal insufficiency confirmed by a test and I'm on glucocorticoids.

I am 18 or older and have never been diagnosed with adrenal insufficiency.

Exclusion Criteria

I regularly use hydrocortisone cream.

I have not taken biotin in the last 3 days.

I have a condition like severe depression, malnutrition, or chronic fatigue that affects my hormone balance.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Cosyntropin Stimulation Test

Participants undergo a cosyntropin stimulation test to measure cortisol levels before and after cosyntropin administration

2 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the cosyntropin stimulation test

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Cosyntropin

Trial Overview

The study aims to find the most accurate cortisol levels for diagnosing adrenal insufficiency using the cosyntropin stimulation test. This will help determine if someone's cortisol levels are too low for daily activities.

How Is the Trial Designed?

Group I: Patients with known adrenal insufficiency Active Control 1 Intervention

This group consists of patients 18 years or older with an established diagnosis of adrenal insufficiency. Study participation by patients with adrenal insufficiency helps us understand what cortisol levels should be, in the new assays, among those with adrenal insufficiency.

Group II: Healthy volunteers Active Control 1 Intervention

Healthy volunteers are those 18 years or older without prior diagnosis of adrenal insufficiency. Study participation by healthy volunteers helps us understand what cortisol levels should be in a healthy population. This information also helps us figure out what levels might be in people with adrenal insufficiency.

Group III: Patients suspected to have adrenal insufficiency Active Control 1 Intervention

This groups consists of patients 18 years or older who are suspected to have adrenal insufficiency. Study participation by this group will help us understand if the cortisol values we get from the new assay accurately diagnose adrenal insufficiency.

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

The synthesized compound [7-Methyltryptophan9]-beta-corticotropin-(1-24) exhibits 2.7 times greater steroidogenic activity compared to beta-corticotropin-(1-24) in isolated adrenal cell bioassays, indicating its potential as a more effective stimulant for steroid production.

This enhanced activity suggests that [7-Methyltryptophan9]-beta-corticotropin-(1-24) could be a promising candidate for further research in therapies targeting adrenal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[7-Methyltryptophan9]-beta-corticotropin-(1-24): a hyperactive Synacthen analogue. Allen, MC., Bailey, PD., Brundish, DE., et al.[2013]

A study involving eight healthy adult men found that a low dose of ACTH(1-24) at 500 ng/1.73 m2 can effectively stimulate adrenal response, similar to the standard short Synacthen test, indicating its potential for assessing adrenal function.

The research demonstrated a dose-dependent increase in plasma cortisol levels, with the timing of peak response being crucial; pretreatment with dexamethasone reduced cortisol response but did not affect peak timing, highlighting the sensitivity of the adrenal response to ACTH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of low doses of ACTH in the investigation of adrenal function in man. Crowley, S., Hindmarsh, PC., Holownia, P., et al.[2019]

Synthetic 1-24 adrenocorticotrophin (tetracosactid) is used for both diagnostic and therapeutic purposes, but it can cause side effects due to overstimulation of the body's hormone production.

A rare but severe case of anaphylactic shock resulting in death occurred in a 14-year-old girl after intravenous administration of tetracosactid, highlighting the need for caution and monitoring during its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fatal complication of intravenous administration of synthetic adrenocorticotrophin]. Müller, M., Fehm, HL., Homoki, J., et al.[2006]

The low dose tetracosactin test (LDT) effectively identifies patients with mild pituitary-adrenal insufficiency, showing similar diagnostic sensitivity to the high dose test (HDT) in a study of 44 patients with pituitary disease and 35 control subjects.

Both the LDT and HDT resulted in plasma tetracosactin levels that maximally stimulate cortisol production, indicating that the LDT can be a viable alternative for assessing adrenal responsiveness without replacing more complex tests like insulin or metyrapone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of low and high dose corticotropin stimulation tests in patients with pituitary disease. Mayenknecht, J., Diederich, S., Bähr, V., et al.[2022]

A single cortisol measurement taken 60 minutes after cosyntropin stimulation is highly effective for screening adrenal insufficiency (AI), showing 99.7% concordance with the traditional multi-timepoint testing method in a study of 702 hospitalized patients.

Using the 60-minute measurement reduces the likelihood of false-positive results compared to a 30-minute measurement, making it a safer and more efficient option for diagnosing AI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single, Post-ACTH Cortisol Measurement to Screen for Adrenal Insufficiency in the Hospitalized Patient. Odom, DC., Gronowski, AM., Odom, E., et al.[2019]

The peptide corticotrophin-(1-23)-tricosipeptide-amide (Acethropan S) effectively assesses adrenal function, showing improved evaluation of cortisol release at a dosage of 0.5 mg compared to 0.25 mg in both normal subjects and patients with adrenal insufficiency.

There were no significant side effects reported from the use of Acethropan S, indicating it is a safe option for evaluating adrenal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Investigation of adrenal function with corticotrophin-(1-23)-tricosipeptide-amide (author's transl)]. Grabner, W., Büchel, CG.[2015]

In a study involving 10 healthy volunteers, the low-dose tetracosactin test (1 microg) showed a significantly slower elimination rate of ACTH compared to the high-dose test (250 microg), suggesting that lower doses may be more suitable for assessing adrenal function.

Despite the differences in ACTH elimination, cortisol production rates were similar between the low-dose and high-dose tests, indicating a maximum adrenal stimulation threshold, which suggests that the low-dose test could be a more appropriate choice for clinical use, pending further research in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile, mean residence time of ACTH and cortisol responses after low and standard ACTH tests in healthy volunteers. Alía, P., Villabona, C., Giménez, O., et al.[2015]

The synthetic corticotrophin analogue alpha(1-18) ACTH shows effective adrenocorticotrophic effects with a prolonged action time of about 24 hours after 0.5 mg and 30 hours after 1 mg, similar to tetracosactrin depot.

Unlike tetracosactrin, alpha(1-18) ACTH is well absorbed when administered intranasally and does not cause painful injection reactions, suggesting it may be a safer and more convenient option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged corticotrophic action of a synthetic substituted 1-18 ACTH. Keenan, J., Thompson, JB., Chamberlain, MA., et al.[2019]

In a study involving 14 healthy neonatal foals, the administration of 10 and 100 micrograms of cosyntropin effectively stimulated cortisol production, making these doses suitable for evaluating adrenal function in foals.

The 1 microgram dose did not significantly increase cortisol levels, while higher doses (100 and 250 micrograms) produced similar peak cortisol concentrations, indicating that lower doses can be effective without the need for higher amounts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthetic adrenocorticotropic hormone stimulation tests in healthy neonatal foals. Hart, KA., Ferguson, DC., Heusner, GL., et al.[2019]

The study compared the effects of low-dose (10 microg) and standard-dose (250 microg) cosyntropin on serum cortisol levels in 83 healthy individuals and 37 patients with various adrenal disorders, finding no significant differences in healthy subjects.

The low-dose cosyntropin test demonstrated better sensitivity for detecting adrenocortical dysfunction, particularly in patients with Addison's disease, suggesting it may be a more effective screening method than the standard dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A high-sensitivity test in the assessment of adrenocortical insufficiency: 10 microg vs 250 microg cosyntropin dose assessment of adrenocortical insufficiency. González-González, JG., De la Garza-Hernández, NE., Mancillas-Adame, LG., et al.[2019]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3262370/

Cosyntropin as a diagnostic agent in the screening ...

20,21 The test has a reported specificity of 95%, with sensitivities of 97%, 57%, and 61% for primary adrenal insufficiency (250 μg cosyntropin test), secondary ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S1470211824046244

Diagnosis and management of adrenal insufficiency

This leaves them vulnerable to steroid deficiency if the medication is stopped suddenly. Regardless of the cause, adrenal insufficiency was invariably fatal ...

3.

karger.com

karger.com/hrp/article/doi/10.1159/000543394/918771/Diagnostic-Utility-of-Low-Dose-Cosyntropin

Diagnostic Utility of Low-Dose Cosyntropin Stimulation ...

Diagnosing central adrenal insufficiency, or adrenocorticotropic hormone (ACTH) deficiency (ACTHD), is often challenging because the signs and ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12535889/

Morning serum cortisol as a predictor of synacthen stimulation ...

Prolonged corticosteroid therapy may result in hypothalamic-pituitary-adrenal (HPA) axis suppression and subsequent adrenal insufficiency ...

5.

mdpi.com

mdpi.com/2075-4418/13/10/1812

Adrenal Failure: An Evidence-Based Diagnostic Approach

Tertiary adrenal insufficiency (TAI) is characterized by hypothalamic anomalies or dysfunction, which results in decreased corticotropin-releasing hormone (CRH) ...

6.

mayoclinic.org

mayoclinic.org/drugs-supplements/cosyntropin-injection-route/description/drg-20562526

Cosyntropin (injection route) - Side effects & uses

Search for a disease or condition . Type 3 or more letters to ... Cosyntropin injection is used to help diagnose adrenal gland problems.

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2024/022028s007lbl.pdf

cosyntropin injection - accessdata.fda.gov

Disease-associated maternal and/or embryo/fetal risk. Unidentified adrenal insufficiency during pregnancy can result in maternal and/or fetal death; therefore, ...

8.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK279122/

Diagnosis and Management of Adrenal Insufficiency - NCBI

Adrenal insufficiency (AI) is a disorder characterized by the failure of adrenocortical function resulting mainly in impaired secretion of glucocorticoids (GCs ...

9.

drugs.com

drugs.com/mtm/cosyntropin.html

Cosyntropin Uses, Side Effects & Warnings

Decadron is used for addison's disease, adrenal insufficiency, adrenocortical insufficiency ... Reviews & ratings. 3.9 / 10. 29 Reviews · View ...