Latent Aging Mechanisms in Pain and Sleep

NCT04683640 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB202000105-NP30AG059297
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic pain is a serious public health problem in older adults depending on the pain condition, and the capacity to sleep properly changes with age. Given the potential mechanistic role of GABA (gamma-aminobutyric acid) in both conditions, based on our preliminary data, this proposal will determine the effect of oral GABA administration in sleep quality and pain in older adults with chronic pain and sleep disorders as well as to characterize the potential neurobiological mechanisms involved in both illnesses.

Conditions

Chronic Pain

Outcome Measures

Primary Outcomes (6)

• The Pittsburgh Sleep Quality Index (PSQI): PSQI Total Score at Baseline

  The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality over the past month. It consists of 19 items grouped into seven components. Each component is scored from 0 to 3, and the component scores are summed to yield a global total score ranging from 0 to 21. Higher scores indicate worse sleep quality. A total score greater than 5 is typically used to distinguish poor sleepers from good sleepers.

  PSQI was administered at baseline

• The Pittsburgh Sleep Quality Index (PSQI): PSQI Total Score at Post-Intervention

  The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality over the past month. It consists of 19 items grouped into seven components. Each component is scored from 0 to 3, and the component scores are summed to yield a global total score ranging from 0 to 21. Higher scores indicate worse sleep quality. A total score greater than 5 is typically used to distinguish poor sleepers from good sleepers.

  PSQI was administered immediately after completing the 4-week intervention

• Verbal Descriptor Scale (VDS) at Baseline

  The Verbal Descriptor Scale (VDS) is a validated self-report measure of pain intensity, commonly used in older adults. Participants are asked to select the descriptor that best represents their current pain level from six options: No pain, Mild, Moderate, Severe, Very severe, and Worst possible pain. Each descriptor corresponds to a numeric value from 0 to 5, with higher scores indicating greater pain intensity.

  VDS was administered at baseline

• Verbal Descriptor Scale (VDS) at Post-Intervention

  The Verbal Descriptor Scale (VDS) is a validated self-report measure of pain intensity, commonly used in older adults. Participants are asked to select the descriptor that best represents their current pain level from six options: No pain, Mild, Moderate, Severe, Very severe, and Worst possible pain. Each descriptor corresponds to a numeric value from 0 to 5, with higher scores indicating greater pain intensity.

  VDS was administered immediately after completing the 4-week intervention

• The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at Baseline

  The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a validated self-report questionnaire that assesses pain, stiffness, and physical function in individuals with musculoskeletal conditions. It includes 24 items scored on a 5-point Likert scale (0 = none to 4 = extreme), producing subscale scores and a total score. The total WOMAC score ranges from 0 to 96, with higher scores indicating worse symptoms and functional limitations.

  WOMAC was administered at baseline.

• The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at Post-Intervention

  The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a validated self-report questionnaire that assesses pain, stiffness, and physical function in individuals with musculoskeletal conditions. It includes 24 items scored on a 5-point Likert scale (0 = none to 4 = extreme), producing subscale scores and a total score. The total WOMAC score ranges from 0 to 96, with higher scores indicating worse symptoms and functional limitations.

  WOMAC was administered after completing the 4-week intervention

Secondary Outcomes (8)

• Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) Total Score at Baseline

  Baseline

• Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) Total Score at Post-Intervention

  Immediately post-intervention (4 weeks)

• Pain Detect at Baseline

  Baseline

• Pain Detect at Post-Intervention

  Immediately post-intervention (4 weeks)

• Functional Outcomes of Sleep Questionnaire - 10 Items (FOSQ-10) at Baseline

  Baseline

Study Arms (2)

Daily Oral GABA

EXPERIMENTAL

You will take, by mouth, 2 pills of GABA (500 mg) (Capsule 250mg) daily at home for 4 weeks

Dietary Supplement: GABA

Daily Placebo

PLACEBO COMPARATOR

You will take, by mouth, 2 pills of Placebo daily at home for 4 weeks

Drug: Placebo

Interventions

GABA DIETARY_SUPPLEMENT

Daily oral GABA for 4 weeks

Also known as: Gamma aminobutyric acid

Daily Oral GABA

Placebo DRUG

Daily oral Placebo for 4 weeks

Daily Placebo

Eligibility Criteria

• Age: 45 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Older adults 45 years of age or older who experienced pain of at least moderate intensity (\>5/10 pain intensity ratings) on more days than not during the past three months, and who also reported poor sleep quality (\>5 PSQI scores) will be considered for participation.

You may not qualify if:

• serious psychiatric conditions (e.g., schizophrenia, major depression, bipolar disorder;
• history of alcohol/drug abuse;
• Alzheimer, Parkinson, Epilepsy and other known intra-cerebral pathology and neurological conditions;
• significant cognitive impairment as evidenced by the Modified Mini-Mental State Examination \[3MS\] score ≤ 77;
• hospitalizations for mental health reasons in the past year;
• chronic/current use of narcotic medications;
• serious systemic (uncontrolled diabetes self-reported HA1C\>7), (uncontrolled hypertension \> 155/90 mm Hg) and rheumatic disorders (i.e., rheumatoid arthritis, systemic lupus erythematosus, fibromyalgia, HIV);
• arterial hypotension;
• digestive tract diseases;
• major medical surgery in the past two months, history of brain surgery or any serious brain condition like aneurysm, stroke, or seizures;
• excessive anxiety regarding protocol procedures;
• Inability to consent for study participation;
• Ingestion of sleep medications including those with zolpidem (Ambien and others) and eszopiclone (Lunesta and others);
• Neuropathic pain medications including anticonvulsants and antidepressants;
• Allergies or sensitivity to GABA or its ingredients cellulose' gelatin (capsule)' magnesium silicate' vegetable stearate and silica or to the placebo or its ingredients: calcium laurate, hypromellose capsule, magnesium (citrate), microcrystalline cellulose;

Sponsors & Collaborators

• University of Florida: lead
• National Institute on Aging (NIA): collaborator
• Thorne HealthTech, Inc: collaborator

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Chronic Pain

Interventions

gamma-Aminobutyric Acid

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

This study was a single-site, proof-of-concept trial with a relatively small sample size, which may limit generalizability. The study remained blinded at the time of reporting; group assignments were not unmasked for outcome comparisons. Some outcome measures had missing post-intervention data, particularly in Group A, potentially impacting statistical power. The adverse event reporting table may reflect minor inconsistencies in total counts due to repeat occurrences per participant.

Results Point of Contact

• Title: Yenisel Cruz-Almeida
• Organization: University of Florida

cryeni@ufl.edu

(352) 294-5845

Study Officials

• Yenisel Cruz-Almeida, MSPH, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2020
• First Posted: December 24, 2020
• Study Start: April 2, 2021
• Primary Completion: May 30, 2024
• Study Completion: May 30, 2024
• Last Updated: July 18, 2025
• Results First Posted: July 18, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)