Clinical trial NCT04927338: Study of Bacopa in Gulf War Illness Patients
Official title: Phase II, Placebo-controlled Study of BacoMind® Bacopa Monnieri Standardized Extract in Gulf War Illness
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Gulf War Illness
Keywords: Veterans
Gulf War Illness
Nutraceutical
Lead sponsor: Nova Southeastern University
Sponsor class: OTHER
Collaborators: name: RTI International
name: Boston University
First posted: 2021-06-16
Enrollment: 170
Sex: ALL
Minimum age (years): 46
Maximum age (years): 78
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a double-blinded, two-arm, placebo-controlled, randomized phase II study in 170 participants born between 1946 and 1978 who are Gulf War Veterans and meet the modified Kansas and Centers for Disease Control and Prevention (CDC) case definition for Gulf War Illness.
Primary purpose: TREATMENT

Brief summary: Gulf War Illness is a condition that affects multiple major organ systems, resulting in a diverse array of symptoms that include debilitating fatigue, memory and cognition difficulties, headaches, sleep disturbances, gastrointestinal problems, skin rashes, and musculoskeletal/joint pain. This phase II, double masked, randomized, placebo-controlled, two-arm study will evaluate cognitive function as evidence of efficacy of the nutraceutical intervention, Bacopa, on central nervous system symptom management of Gulf War Illness, along with assessments of safety of the intervention.

Detailed description: This is a study in Gulf War Veterans born between 1946 and 1978 who meet the modified Kansas and Centers for Disease Control and Prevention (CDC) case definitions for Gulf War Illness. This phase II, double-masked, randomized, placebo-controlled, two-arm study will focus on assessing cognitive function as evidence of efficacy of the nutraceutical intervention, Bacopa, on central nervous system symptom management of Gulf War Illness. 170 participants will be randomized 1:1 to receive either 12 weeks of the intervention (Bacopa) or placebo. Participants will be evaluated "remotely" via online assessment tools and telephone interviews, allowing participation from a nationwide catchment area. Primary assessment via the California Verbal Learning Test, Second Edition (CVLT-II) will occur at baseline and 12 weeks, along with laboratory assessments for all participants at baseline, and a self-selected subgroup at 12 weeks. Randomization to the intervention or placebo arms will be stratified by membership in the 12-week follow-up laboratory subgroup and sex. Laboratory draws will be performed at the participant's local clinical laboratory and will allow for measurements of putative biomarkers of neuron health and structural integrity along with biomarkers of inflammation and immune signaling. Monitoring phone calls will be made to the participant biweekly to assess safety. Participants will also undergo subjective assessments of physical health, vitality, sleep, pain, and symptom severity at baseline, 6, 12, and 16 weeks. Thus, participants will be observed through the treatment period (12 weeks) and for 4 weeks after completion to assess immediate effects and durability of the response.

Eligibility criteria: Inclusion Criteria:

1. Born in years 1942 to1978
2. Served in the Gulf War theater for any period between August 1990 and July 1991
3. Meets modified Kansas case definition criteria and CDC case definition for Gulf War Illness (GWI). The modified Kansas definition, which includes the CDC criteria includes:

   1. Allowance for normal illnesses of aging, such as hypertension and diabetes if the conditions are treated and are in demonstrable stable and normal ranges at the time of screening and assessment.
   2. Allowance of stable comorbid conditions such as post-traumatic stress disorder (PTSD), major depressive disorder (MDD), and traumatic brain injury (TBI) that have not required hospitalization in the 5 years prior to recruitment. Severe TBI is excluded.
4. Able to consent to the study
5. Participants of childbearing potential must practice effective contraception during the study so that, in the opinion of the Investigator, they will be compliant with birth control measures during the study.
6. Agrees to participate in follow-up visits.

Exclusion Criteria:

1. They are scheduled for a surgery during the period of study participation, had minor surgery within 3 months prior to screening, or had major surgery within 6 months prior to screening,
2. Self-report of current untreated major depression with psychotic or melancholic features (as determined by self-report), schizophrenia, bipolar disorder, delusional disorders, dementias of any type, or substance abuse during the last two years (excluding cannabis products),
3. Any serious allergic disease (self-report), possibly resulting in anaphylaxis, such as food/drug allergies, including allergic asthma, or allergy to any ingredient of the active product or placebo, including allergies to FD\&C Yellow No. 5 (tartrazine),
4. Renal disease (self-report; laboratory results: renal insufficiency with serum creatinine \> 2.0 mg/dL or eGFR \< 44; or currently on renal dialysis),
5. Hepatic insufficiency (bilirubin \>2.5mg/dL or transaminases \>3x the upper limit of normal (ULN)). Participants with Gilberts syndrome are eligible for the study if other liver function tests are normal, regardless of bilirubin level,
6. Pregnancy (premenopausal female participants),
7. Current heavy alcohol or tobacco use (self-report). Heavy use is defined as alcohol consumption not to exceed approximately 15 drinks per week (with a drink defined as 12 oz beer, 5 oz wine, or 1.5 oz distilled spirits) and tobacco use not to exceed 20 cigarettes (or equivalent) per day.
8. Current exclusionary diagnosis that could reasonably explain the symptoms of their fatiguing illness and their severity, using the exclusion criteria best described in the Ambiguities in case definition paper for Chronic Fatigue Syndrome (CFS), as described in detail in Reeves et al., 2003, which clarifies exclusionary conditions. Specifically, the exclusionary diagnoses that are not otherwise listed above comprise:

   * organ failure (e.g., emphysema, cirrhosis, cardiac failure, chronic renal failure)
   * chronic infections (e.g., AIDS, hepatitis B or C) or inflammatory bowel disease (IBD) (via self report)
   * major neurologic diseases that could cause fatigue or neurologic deficits such as (e.g., epilepsy, stroke, brain tumor, multiple sclerosis, Parkinson's Disease, Alzheimer's disease) or history of CNS demyelinating disease (e.g., multiple sclerosis, neuromyelitis optica spectrum disorder) (Self report),
   * cancer or cancer treatment (e.g., chemotherapy, radiation of brain), or current use of biologic modifiers that could affect immune function (e.g., Etanercept, Rituximab) (self-report)
   * untreated primary sleep disorders (e.g., sleep apnea, narcolepsy)
   * uncontrolled diabetes (HgbA1c \> 7)
9. Temporary conditions discovered at screening for which participants may be rescreened 6 weeks after resolution of condition.

   * Temporary effects of medications
   * Temporary sleep deprivation
   * Untreated hypothyroidism/hyperthyroidism, hypothyroidism/hyperthyroidism that has been inadequately controlled during the last 3 months, or free T4 level not within normal limit
   * Active infection
10. Participating in another interventional clinical trial of an investigational therapy (including social-behavioral therapy) within 6 weeks prior to consent to participate in this study, or planning to participate in another interventional clinical trial of an investigational therapy during this study,
11. Use of Bacopa within 6 weeks prior to the enrollment in this study,
12. Diagnosed bleeding disorder or current use of anticoagulants and/or antiplatelets, except for low dose nonsteroidal anti-inflammatories (NSAIDS).

Primary outcomes:
measure: California Verbal Learning Test (CVLT-II) Assessment
timeFrame: 12 weeks
Secondary outcomes:
measure: Blood Biomarker Concentrations
timeFrame: 12 weeks
measure: Veterans RAND 36 Item Health Survey (VR-36©)
timeFrame: 12 weeks
measure: Veterans RAND 36 Item Health Survey (VR-36©)
timeFrame: 16 weeks
measure: Review of Treatment Related Adverse Events
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Davie
country: United States
facility: Nova Southeastern University
state: Florida
Study officials:
affiliation: Nova Southeastern Univeristy
name: Amanpreet Cheema, PhD
role: PRINCIPAL_INVESTIGATOR
References: