Amino Acid Blend for Delirium

Overseen By Gohar Azhar, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Arkansas

Disqualifiers: Chronic kidney disease, Major psychiatric illness, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 days

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special blend of amino acids to determine if it can prevent or reduce delirium in older adults hospitalized with certain infections. Delirium is a sudden change in the brain that causes confusion. Some participants will receive the amino acid blend (referred to as the 260279 active study product), while others will receive standard hospital care. The trial seeks individuals aged 60 and older who are hospitalized with infections like pneumonia or urinary tract infections and are experiencing delirium or confusion. As an unphased trial, this study provides a unique opportunity to contribute to research that could improve care for older adults facing delirium.

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

The trial protocol does not specify if you need to stop taking your current medications. It seems likely that you can continue them, but please confirm with the trial coordinators.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that amino acids, which help form proteins, are usually easy for the body to handle. Participants in previous trials with similar amino acid supplements mostly experienced minor side effects, such as an upset stomach. However, the mix of amino acids in this trial is new.

The trial is marked as "Not Applicable" for phases, indicating it hasn't been fully tested in humans yet. Therefore, limited information exists on how people might react to this specific mix. Still, since amino acids are common in many foods and supplements, there is some confidence in their general safety. Consulting a healthcare provider is always advisable to understand any potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for delirium?

Most treatments for delirium focus on managing symptoms with antipsychotics or sedatives. However, the amino acid blend being studied is unique because it offers a nutritional approach, potentially addressing delirium by supporting brain function and recovery through essential nutrients. Researchers are excited about this treatment since it uses an oral amino-acid supplement, providing a non-invasive and possibly faster-acting alternative. This innovative approach could complement existing treatments, offering a new pathway for managing delirium effectively.

What evidence suggests that this amino acid blend might be an effective treatment for delirium?

Research shows that certain mixtures of amino acids might improve health in hospitalized patients, especially those in critical care. In this trial, some participants will receive an oral amino-acid-containing nutritional supplement. Previous studies have found this supplement aids muscle and gut health in ICU patients. Amino acids are crucial because they build proteins, supporting the body's recovery. This mix might also reduce or prevent confusion in older adults by providing nutrients that support brain health. Although complete proof for its effect on confusion is not yet available, the mix's success in other health areas is promising. ^{1 2 3 6 7}

Who Is on the Research Team?

Gohar Azhar, M.D.

Principal Investigator

University of Arkansas

Are You a Good Fit for This Trial?

This trial is for hospitalized individuals aged 60 or older with delirium due to infections like sepsis, pneumonia, UTI, bone/tissue infection, or fever of unknown origin. It excludes those with chronic kidney disease, recent major surgery, uncontrolled psychiatric illness, suspected COVID-19, and delirium from substance withdrawal.

Inclusion Criteria

I am 60 or older with a current diagnosis of a serious infection.

I am 60 or older, currently hospitalized with an infection or fever, and have experienced confusion or altered mental status.

Exclusion Criteria

My kidney function is severely reduced.

I have been hospitalized for a serious mental health issue.

My mental health condition is well-managed with medication or treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either the amino acid supplement or standard treatment for up to 4 days

4 days

Daily visits for cognitive assessments and blood draws

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• 260279 active study product
• 260279 placebo

Trial Overview The study tests a special amino acid blend thought to prevent or lessen delirium severity against a placebo (sugar water). Of the up to 45 participants enrolled: 15 will take the blend twice daily for four days; another 15 will have the placebo; and the remaining are non-delirious controls not consuming any product.

How Is the Trial Designed?

Group I: Control group Active Control 1 Intervention

Delirious control group and non-delirious control group who receives standard treatment in the hospital.

Group II: Delirious subjects receiving active study product Active Control 1 Intervention

Subjects will ingest an oral amino-acid containing nutritional supplement twice daily for up to 4 days.

Who Is Running the Clinical Trial?

University of Arkansas

Lead Sponsor

Trials

500

Recruited

153,000+

Published Research Related to This Trial

In a pilot study involving six healthy female volunteers, a modified amino acid mixture successfully reduced plasma tryptophan levels to 21% of baseline, indicating its potential effectiveness in serotonin function research.

The amino acid mixture was well-tolerated, with minimal side effects reported, suggesting it could be a safe tool for future studies assessing behavioral responses to tryptophan depletion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the effects of amino acid mixture and placebo on plasma tryptophan to large neutral amino acid ratio. Wolfe, BE., Metzger, ED., Jimerson, DC.[2019]

In a pilot study involving 6 children and adolescents with tardive dyskinesia (TD), a 2-week treatment with branched chain amino acids (BCAA) resulted in significant symptom reductions of 40% to 65% in 5 out of 6 participants.

The promising results and good tolerability of BCAA suggest it could be a viable treatment option for TD in younger populations, indicating a need for further large-scale studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Branched chain amino acid treatment of tardive dyskinesia in children and adolescents. Richardson, MA., Small, AM., Read, LL., et al.[2022]

Sodium benzoate, when added to treatment for schizophrenia, significantly improves positive symptoms but does not have a beneficial effect on negative symptoms, cognitive function, or overall quality of life, based on a meta-analysis of four studies.

Patients receiving sodium benzoate experienced a higher incidence of extrapyramidal symptoms compared to the control group, indicating potential safety concerns despite its efficacy in addressing positive symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of add-on sodium benzoate, a D-amino acid oxidase inhibitor, in treatment of schizophrenia: A systematic review and meta-analysis. Seetharam, JC., Maiti, R., Mishra, A., et al.[2022]

In a 4-week study involving about 40 in-patients, adding a tailored amino acid mixture to the antidepressant Remeron significantly improved depression symptoms compared to a placebo.

The amino acid treatment showed no side effects, which may enhance patient compliance and improve the overall benefit/risk ratio of the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Add-On"-therapy with an individualized preparation consisting of free amino acids for patients with a major depression. Ille, R., Spona, J., Zickl, M., et al.[2018]

Branched-chain amino acids significantly reduced tardive dyskinesia symptoms in psychiatric patients, with a notable improvement observed in 36% of participants after 3 weeks of treatment compared to placebo.

The treatment was found to be safe, with minimal gastrointestinal side effects and no significant changes in physical examinations or laboratory tests, suggesting a novel approach to managing tardive dyskinesia without altering antipsychotic medication levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of the branched-chain amino acids in the treatment of tardive dyskinesia in men. Richardson, MA., Bevans, ML., Read, LL., et al.[2007]

In a randomized double-blind study involving 59 patients with schizophrenia, the addition of 2g of sarcosine to ongoing antipsychotic treatment showed no significant effects on cardiometabolic or body composition parameters over 6 months.

This study is the first of its kind to assess the metabolic safety of sarcosine in schizophrenia patients, highlighting its potential safety in a population that often experiences metabolic abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No changes of cardiometabolic and body composition parameters after 6-month add-on treatment with sarcosine in patients with schizophrenia. Strzelecki, D., Kałużyńska, O., Szyburska, J., et al.[2018]

In a 12-week study involving chronic schizophrenia patients, the combination of sarcosine and sodium benzoate significantly improved cognitive and global functioning compared to sarcosine alone, even when clinical symptoms did not improve.

This suggests that enhancing NMDA receptor activity through dual inhibition of GlyT-1 and DAAO can specifically target cognitive deficits in schizophrenia, highlighting a potential new approach for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive sarcosine plus benzoate improved cognitive function in chronic schizophrenia patients with constant clinical symptoms: A randomised, double-blind, placebo-controlled trial. Lin, CY., Liang, SY., Chang, YC., et al.[2018]

The new amino acid mixture for treating hyperphenylalaninemia has been found to be safe and well tolerated after over a year of clinical testing as a beverage.

While the mixture can be easily incorporated into various foods without altering taste, it does not provide better control of plasma phenylalanine levels compared to other existing products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new amino acid mixture permits new approaches to the treatment of phenylketonuria. Buist, NR., Prince, AP., Huntington, KL., et al.[2019]

Intravenous infusion of leucine significantly reduces levels of aromatic amino acids and methionine, while valine and isoleucine do not have this effect, indicating leucine's unique mechanism of action.

A mixture of branched-chain amino acids, primarily containing leucine, shows similar effects to leucine alone and may be beneficial for treating patients with hepatic cirrhosis and encephalopathy, based on the study of healthy volunteers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of the effects of intravenous infusion of individual branched-chain amino acids on blood amino acid levels in man. Eriksson, S., Hagenfeldt, L., Wahren, J.[2019]

Chronic treatment with d-alanine improved symptoms in schizophrenia, suggesting that NMDAR hypofunction may play a role in cognitive decline and psychosis.

However, in a study with dogs, coadministration of sodium benzoate did not increase d-alanine levels in the cerebral spinal fluid, indicating that sodium benzoate's clinical benefits in schizophrenia and Alzheimer's may not be due to DAAO inhibition as previously thought.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of Effect of Sodium Benzoate at Reported Clinical Therapeutic Concentration on d-Alanine Metabolism in Dogs. Popiolek, M., Tierney, B., Steyn, SJ., et al.[2019]

D-alanine, when used as an add-on therapy for schizophrenia, can improve symptoms but requires high doses (~7 g) due to potential oxidation by D-amino acid oxidase (DAAO).

In a study with baboons, co-administration of a DAAO inhibitor (CBIO) increased plasma levels of D-alanine but did not significantly enhance its levels in the cerebrospinal fluid (CSF), raising concerns about the effectiveness of DAAO inhibition for increasing D-alanine exposure in treating schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral administration of D-alanine in monkeys robustly increases plasma and cerebrospinal fluid levels but experimental D-amino acid oxidase inhibitors had minimal effect. Rojas, C., Alt, J., Ator, NA., et al.[2018]

In a study of 87 patients with varying levels of metabolic stress after major surgery or trauma, a branched chain enriched amino acid formula (MAA) showed better nitrogen retention compared to a standard amino acid formula (SAA) over a 7-day period.

The MAA group achieved nitrogen equilibrium at lower doses and had reduced urinary nitrogen excretion, indicating that branched chain amino acids are more effective in promoting nitrogen retention, especially in patients experiencing higher levels of metabolic stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of stress level, amino acid formula, and nitrogen dose on nitrogen retention in traumatic and septic stress. Cerra, F., Blackburn, G., Hirsch, J., et al.[2019]

Ingesting branched-chain amino acids (BCAAs) like leucine, isoleucine, and valine significantly affects plasma amino acid profiles, with leucine causing a rapid increase in its levels peaking around 30 minutes after ingestion.

Leucine not only elevates its own concentration but also regulates the levels of other amino acids, such as methionine and phenylalanine, while isoleucine and valine primarily increase without affecting other amino acids significantly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bolus ingestion of individual branched-chain amino acids alters plasma amino acid profiles in young healthy men. Matsumoto, T., Nakamura, K., Matsumoto, H., et al.[2020]

In a study of 65 patients with cirrhosis and acute hepatic encephalopathy, the infusion of a branched chain enriched amino acid mixture did not improve the prognosis for recovery compared to glucose, with similar wake-up rates in both groups (17 patients each).

However, the amino acid group showed a reversal of negative nitrogen balance, indicating potential benefits for nitrogen homeostasis, despite a higher mortality rate and worsening coma scores in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Branched chain enriched amino acid versus glucose treatment of hepatic encephalopathy. A double-blind study of 65 patients with cirrhosis. Vilstrup, H., Gluud, C., Hardt, F., et al.[2019]

In a study of 70 cirrhotic patients with acute hepatic encephalopathy, the use of a modified amino acid solution did not show significant clinical improvement compared to a standard amino acid solution over a 5-day treatment period.

Both treatment groups had similar outcomes, with no significant differences in patient improvement or deterioration, indicating that modified amino acid solutions are ineffective for treating acute hepatic encephalopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of acute hepatic encephalopathy in cirrhotics with a branched-chain amino acids enriched versus a conventional amino acids mixture. A controlled study of 70 patients. Michel, H., Bories, P., Aubin, JP., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05066503?tab=history&a=3

Nutritional Therapy for Delirium in Elderly Hospitalized Subjects Dietary Supplement: 260279 active study product. The active study product (20g per serving) contains 13.6g of amino acids and natural flavors, citric acid ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05066503

Nutritional Therapy for Delirium in Elderly Hospitalized ... The investigators have developed a proprietary blend of amino acids that they think will help to prevent or reduce the severity of delirium in older adults (60 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10964107/

Paradigms and Success Stories of Natural Products in ... Natural therapy for delirium in elderly hospitalized subjects, Dietary Supplement: 260279 active study product, Arkansas, 45, Not applicable, Recruiting, March ...

4. cdek.crib.liu.edu cdek.crib.liu.edu/trial/NCT02968836/

Trial | NCT02968836 Assessment of the Safety and efficacy of an amino acid blend on muscle and gut functionality in Intensive Care Unit (ICU) patients.

5. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT02968836?keyword=%22Nutrition%22

Safety and Efficacy of an Amino Acid Blend on Muscle and ... Effect of an enteral amino acid blend on muscle and gut functionality in critically ill patients: a proof-of-concept randomized controlled trial. Crit Care.

6. sciencedirect.com sciencedirect.com/science/article/pii/S0928098722001385

Lipid based intramuscular long-acting injectables This review will discuss all relevant aspects related to the development of lipid-based long acting injectables with a special focus on intramuscular (IM) ...

7. ueaeprints.uea.ac.uk ueaeprints.uea.ac.uk/85955/1/Wilkinson_etal_2022_EJoPS.pdf

Lipid based intramuscular long-acting injectables Clinical evidence has shown significantly improved key therapeutic markers such as reduction of relapses in the case of schizophrenia patients.