Gut bacteria in Huntington disease

Investigating the Role of the Gut Microbiome in Huntington's Disease

This project will try to see if adults with Huntington's disease who worsen quickly have different gut bacteria than those who progress more slowly.

Quick facts

• Study type: Observational
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Central Florida (Academic / other)
• Drugs / interventions: chemotherapy, Methotrexate
• Locations: 1 site (Orlando, Florida)
• Trial ID: NCT06448546 on ClinicalTrials.gov

What this trial studies

This observational study will compare the gut microbiome of adults with clinically confirmed adult-onset Huntington disease across groups defined by body mass index and recent involuntary weight change, and with a control group with normal CAG repeat length. Participants will provide medical history, UHDRS-based clinical staging, CAG repeat information, and stool samples for microbiome sequencing, along with metabolic and weight measurements. The goal is to identify whether distinct gut bacterial populations correlate with faster versus slower clinical progression and with obesity or pathological weight loss. Recruitment and visits occur at the University of Central Florida in Orlando.

Who should consider this trial

Good fit: Ideal candidates are adults (18+) with adult-onset HD (CAG 40–59), documented clinical diagnosis with high confidence on the UHDRS, in Functional Assessment stages I–III, who are underweight with recent loss or overweight/obese or have unexplained recent weight gain, plus separate healthy controls with CAG ≤26 and normal BMI.

Not a fit: People with juvenile-onset or very advanced HD, CAG repeat lengths outside the specified ranges, inability to comply with visit/sample requirements, or who cannot read English are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, the work could point to gut bacteria linked to HD progression and suggest new directions for dietary, microbial, or metabolic interventions.

How similar studies have performed: Animal studies and early human microbiome reports suggest gut–brain links and altered gut bacteria in HD, but robust human evidence is limited and this approach remains preliminary.

Eligibility criteria

* Inclusion Criteria:

  * 18 years or older
  * Provide informed consent
  * Able to read and speak English
  * Agree to comply with study procedures
* Inclusion criteria for the control group include:

  * CAG repeat length ≤ 26.
  * BMI 18.5-24.9
* Inclusion criteria for experimental group 1 include:

  * BMI \< 18.5 (underweight) or significant, involuntary weight loss within the past 12 months.
  * CAG repeat length 40 - 59.
  * Documentation of the Clinical Diagnosis of HD with a high level of certainty (\>99% confidence) using the validated Unified Huntington's Disease Rating Scale (UHDRS).
  * Stage I-III on the Functional Assessment component of the UHDRS
* Inclusion criteria for experimental group 2 include:

  * BMI \> 25.0 (overweight - obesity) or BMI ≤ 25.0 with significant, unexplained weight gain within the past 12 months
  * CAG repeat length 40 - 59.
  * Documentation of the Clinical Diagnosis of HD with a high level of certainty (\>99% confidence) using the validated UHDRS.
  * Stage I-III on the Functional Assessment component of the UHDRS
* Exclusion Criteria:

  * CAG repeat length ≥ 60 to exclude participants with juvenile onset HD.
  * CAG repeat length 36 - 39 to exclude participants with reduced penetrance. As this is a pilot study, we are primarily interested in participants with typical HD characteristics.
  * UHDRS Functional Capacity stage ≥ 4 to exclude late-stage HD patients who may be institutionalized and receive nutrition through a feeding tube.
  * Use of any of the following drugs within the last 6 months:

    * System antibiotics, antifungals, antivirals, or anti-parasitics (intravenous, intramuscular, or oral)
    * Corticosteroids (intravenous, intramuscular, oral, nasal, or inhaled)
    * Cytokines
    * Methotrexate, immunosuppressive cytotoxic agents, or chemotherapy
    * Commercial probiotics ≥ 100 million CFU (fermented foods, yogurts, and other homeopathic probiotics and prebiotics do not apply)
  * Use of topical antibiotics or topical steroids within the last 7 days
  * History of active, uncontrolled gastrointestinal disorders or diseases, including:

    * Inflammatory bowel disease
    * Ulcerative colitis
    * Crohn's disease
    * Irritable bowel syndrome
    * Infectious gastroenteritis, colitis, or gastritis
    * Clostridium difficile or Helicobacter pylori infection
    * Persistent or chronic constipation or diarrhea
  * Acute illness with or without fever at time of sample collection
  * Positive for HIV, hepatitis B, or hepatitis C
  * Confirmed or suspected immunodeficient condition/state
  * Major surgery of the GI tract, excluding cholecystectomy and appendectomy
  * Unstable dietary history within the past month, such as elimination or significant increase of a major food group in the diet
  * Recent history of chronic, excessive alcohol consumption
  * Travel outside of the United States within the last 3 months

Where this trial is running

Orlando, Florida

• University of Central Florida — Orlando, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Amber Southwell, PhD — University of Central Florida
• Study coordinator: Amoy Fraser, PhD, CCRP, PMP

Conditions Huntington Disease; HD; Gut Microbiome