Longitudinal Evaluation of Short-Chain Fatty Acid Profiles During the Natural Disease Course and a Mediterranean Diet Intervention in Amyotrophic Lateral Sclerosis Patients

NCT07178067 | Completed DMC

• 2 other identifiers: TE 74/2022PN-III-P1-1.1-TE-2021-0960
• Study Type: observational
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This observational study explored the connection between the gut microbiota and the brain in patients with amyotrophic lateral sclerosis (ALS), specifically the modulation of short-chain fatty acids during disease progression and after following a Mediterranean diet for 6 months. Recent research suggests that the gut microbiome-the community of bacteria and other microorganisms living in our intestines-may influence how ALS develops and progresses. The hypothesis was that changes in the gut microbiome and the substances it produces, such as short-chain fatty acids (SCFAs), may play an important role in ALS progression. Additionally, the effect of the Mediterranean diet on circulating short-chain fatty acid concentrations was assessed.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

short-chain fatty acid; amyotrophic lateral sclerosis; microbiota-gut-brain axis; LC-MS/MS

Outcome Measures

Primary Outcomes (1)

• Analysis of serum SCFA levels in ALS patients and healthy controls, and evaluating the change in circulating SCFA concentrations associated with Mediterranean diet intervention

  This study compares plasma levels of short-chain fatty acids (SCFAs): acetic acid (ng/mL), propanoic acid (ng/mL), butyric acid (ng/mL), 3-OH butyric acid, 4-methyl-valeric acid (ng/mL) between adults with amyotrophic lateral sclerosis (ALS) and age/sex-matched healthy controls at baseline (T0) and then tracks how these levels change after 6 months of natural disease progression (T1) and 6 months after introducing a Mediterranean diet (T2) in ALS patients. Outcomes: Mean SCFA concentrations (±SD) (ng/mL) at T0 between-group (ALS vs control) differences at baseline, and within-patient changes over time to assess whether the Mediterranean diet is associated with favorable SCFA shifts (T0-T1, T1-T2).

  12 months

Secondary Outcomes (1)

• Association of Serum SCFA Levels With ALS Progression Measured by ALSFRS-R at T0, T1, and T2

  12 months

Study Arms (1)

ALS patients

44 patients diagnosed with amyotrophic lateral sclerosis (ALS) in the past 12 months.

Other: Mediterranean diet

Interventions

Mediterranean diet OTHER

The Mediterranean diet, characterised by a high intake of fruits, vegetables, whole grains, legumes, nuts, and olive oil, along with moderate consumption of fish and poultry, has been associated with anti-inflammatory and neuroprotective effects. Notably, this dietary pattern has the potential to enhance the production of short-chain fatty acids (SCFAs) and support gut microbial diversity, representing a promising strategy for nutritional intervention in patients with ALS.

ALS patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This prospective, single-center study enrolled adults from Romania diagnosed with ALS at Neurology Clinic 1, Mureș County Clinical Emergency Hospital , with an ALS diagnosis within the past 12 months, disease duration under 1 year, El Escorial (1996) criteria-clinically probable or clinically definite ALS. ALS cohort: N=44 at baseline (T0, Aug-Oct 2022); mean age 58.4 ± 12.5 years; 28 men / 16 women. Follow-up: T1 (6 months): N=36 (8 deaths by T1). T2 (12 months): N=30 (6 additional deaths between T1 and T2). Healthy controls: N=40, age- and sex-matched community volunteers without known neurodegenerative or major systemic disease. The patients were recruited through consecutive recruitment at the Neurology Clinic 1, Mureș County Clinical Emergency Hospital (Târgu Mureș, Romania) over a 3-month window (01 Aug-31 Oct 2022).

You may qualify if:

• Patients diagnosed with amyotrophic lateral sclerosis (ALS) in the past 12 months.
• Disease duration of less than 1 year.
• Fulfillment of the El Escorial diagnostic criteria (1996) for clinically probable or clinically definite ALS.

You may not qualify if:

• Patients with an expected survival \<18 months.
• Presence of other neurodegenerative diseases.
• Major comorbidities, such as: heart failure, cancer, autoimmune diseases, systemic diseases.
• Gastrointestinal diseases that could influence gut microbiota.
• Recent or ongoing treatment with antibiotics, probiotics, or prebiotics.
• Low compliance with study procedures.

Sponsors & Collaborators

• George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures: lead

Study Sites (1)

University of Medicine, Pharmacy, Science and Technology of Târgu Mureș 'George Emil Palade'

Târgu Mureş, Mureș County, 540142, Romania

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood samples

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Diet, Mediterranean

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet, Plant-Based; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 3, 2025
• First Posted: September 17, 2025
• Study Start: July 21, 2022
• Primary Completion: November 30, 2023
• Study Completion: November 30, 2023
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

RO (1)