Clinical trial NCT05467904: Double-Blind Randomized Placebo-Controlled Trial of a Proprietary Full Hemp Flower Formulation for Long COVID
Official title: A Double-Blind Randomized, Placebo-Controlled Trial of a Proprietary Full Hemp Flower Formulation ( Xltran™ and Xltranplus™) to Determine Clinical Improvement in the Syndrome of Long COVID
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Post-acute COVID-19 Syndrome
Lead sponsor: Bateman Horne Center
Sponsor class: OTHER
Collaborators: name: Endourage, LLC
First posted: 2022-07-21
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a double-blind, randomized, placebo-controlled single-center clinical trial to explore the safety and efficacy of a full cannabis flower formulation, rich in cannabinoids and terpenes formulation, Xltran Plus™ and Xltran™, both compared to placebo for the treatment of Long COVID patients with prolonged symptoms caused by COVID-19.

Detailed description: This is a double-blind, randomized, placebo-controlled single-center, 28-day study designed to explore the safety and efficacy of Xltran Plus™ and Xltran™ for the treatment of Long COVID in adults. The treatment consists of daily doses of Xltran Plus™, Xltran™, or placebo. Xltran Plus™ contains 10.42 mg of cannabinoids, 0.55 mg tetrahydrocannabinol (THC), and 2.729 mg of terpenes per 0.25 ml of solution. Xltran™ contains 0 mg of cannabinoids, 0 mg THC and 1.28 mg terpene per 0.25 ml of solution. Placebo contains water, sunflower lecithin and polysorbate. Trial participants will be randomized to Xltran Plus™, Xltran™ or placebo at Visit 1. Participants will take 1 ml sublingually after morning meal and 1 ml sublingually after the evening meal for 28 days.

There will be 111 patients with Long COVID enrolled. There will be approximately 37 patients randomized to each arm.

Candidates will undergo initial pre-screening by telephone, after which, if they appear to meet initial entry criteria, will be invited for an in-person visit. The first visit, Visit 1, will include vitals, symptom questionnaires, cognitive testing, and urine and blood sampling. Participants will receive weekly symptom surveys to complete online. Each participant will be instructed on cognitive testing using their smart phone and complete the cognitive testing weekly.

Patients with underlying medical or psychiatric conditions that could impact their safe participation in the study or interfere with their ability to complete or comply with the study's requirements will not be enrolled. Patients on active illicit or non-prescribed drug use and chronic, daily use of an immune suppressant (e.g., prednisone) will be excluded. Patients with documented history and active treatment for seizure disorder, and any condition that in the opinion of the investigator would be harmful or detrimental to the patient will not be enrolled in the study.

Patients may remain on stable doses of opioids, SSRIs and other anti-depressants; however, poorly controlled, or severely depressed patients will not be enrolled. Only clinically stable and well-controlled patients will be considered.

At Visit 1, the PI will ensure that all entry criteria have been satisfied and the participant will be randomized and initiate treatment with one dose on the day of the Visit 1 (Day 1), followed by BID dosing for the duration of the study.

Urine will be collected at Visit 1 for pregnancy testing. Urine drug screening for drugs of abuse will be conducted at Visit 1; patients positive for cocaine, methamphetamine, phencyclidine (PCP), methadone, non-disclosed opiates, or marijuana metabolites should be screen failed. Patients positive for disclosed, stable doses of prescribed opioids are able and may remain on these medications during the study. Additional drug testing may be conducted at the investigator's discretion.

A blood sample will be collected at Day 1 (Visit 1) and Day 28 (Visit 2) for changes in inflammatory markers.

Patients will receive assigned study treatment for a total of 28 days, with treatment dispensed at Visit 1 (Day 1) and the amount of treatment remaining, if any, accounted for at Visit 2 (Day 28) end of treatment visit.

At the end of the trial and after results are unblinded, those who received placebo will be provided with a 28-day supply each of Xltran Plus™ and Xltran™ if they are interested.

Eligibility criteria: Inclusion Criteria:

1. Willing and able to read, understand, and sign the informed consent
2. Diagnosis of Long COVID is defined as the following:

   1. Infected individuals will have a confirmed SARS-CoV-2 infection within 36 months of enrollment and have had at least one month of persistent fatigue and muscle weakness, functional impairment, and cognitive impairment since the acute infection.
   2. Adults with confirmed prior SARS-CoV-2 infection will satisfy any one of the following:

   i. Any person with a positive SARS-CoV-2 polymerase chain reaction (PCR) or nucleic acid amplification test (NAAT); ii. Any person with a positive SARS-CoV-2 antigen rapid diagnostic test; iii. Any person with a positive SARS-CoV-2 antibody test
3. Male and female patients, 18-65 years of age

   a. Female patients of child-bearing potential must have a negative urine pregnancy test at Visit 1. Women confirmed to be of non-childbearing potential do not require pregnancy testing. To be considered of non-child-bearing potential, the patient must be: i. Post-menopausal (defined as no menses for at least one year); or ii. Surgically sterile (s/p hysterectomy, bilateral oophorectomy, or bilateral tubal ligation at least six months prior to beginning treatment with study product); or iii. At least three months s/p a non-surgical permanent sterilization procedure b. Females of child-bearing potential must be willing to utilize an effective birth control method for the duration of the study. Women involved in monogamous same-sex relationships or committed to sexual abstinence (e.g., religious reasons) will be waived from this requirement. Allowable contraceptive methods include: i. Oral, implantable, injectable, or transdermal hormonal contraceptives (should have been used for a minimum of one full cycle prior to administration of study product) ii. Intrauterine devices (IUD) iii. Vasectomized partner iv. Double barrier method (male or female condom, sponge, diaphragm, or vaginal ring with simultaneous use of spermicidal jelly or cream)
4. A urine drug screen performed at the Visit 1 must be negative for drugs of abuse such as methamphetamine, cocaine, phencyclidine (PCP), marijuana metabolites, and non-disclosed amphetamines and opioids/opiates. The following stipulations also apply:

   a. Patients with a positive screening UDS due to prescribed amphetamines for allowed conditions do not require further UDS testing. They may proceed with study treatment, assuming no evidence of abuse or dependency.
5. Patients should not require treatment with warfarin, heparin, lithium, digoxin, amiodarone, isoniazid, phenytoin, fluconazole, methotrexate, probenecid, or raloxifene. Patients on these medications should not be screened.
6. Patients agree to refrain from taking medications that would affect assessment of the effectiveness of study product for the duration of the study
7. Willing and able to comply with all protocol-specified requirements
8. Have a smart phone and internet access to complete online surveys and cognitive testing

   Exclusion Criteria:
9. Improvement in fatigue and physical function because of any treatment intervention in the past month
10. Use of Xltran Plus™ or Xltran™ within 30 days of Visit 1.
11. Current use of marijuana or medical cannabis
12. Currently receiving chronic/daily systemic corticosteroids (\>5 mg prednisone daily, or equivalent)
13. BMI \<20 or \>40
14. Breastfeeding or pregnant, or planning to become pregnant during the next six months
15. In the opinion of the Investigator, any clinically significant, uncontrolled, or unstable medical or surgical condition that could affect the patient's ability to participate in the study or potentially compromise their well-being while enrolled in the study

    a. Symptomatic and/or otherwise clinically significant cardiac disease, including but not limited to: myocardial infarction during the preceding two years; uncontrolled hypertension; symptomatic heart failure (e.g., New York Heart Association Class II or higher); angina or other evidence of significant coronary artery disease; or anticipation of bypass or other cardiac surgery within the next 12 months
16. In the opinion of the Investigator, evidence of a clinically significant psychiatric disorder; e.g., severe, unstable or poorly controlled depression, anxiety or obsessive-compulsive disorder; moderate or severe alcohol use disorder; substance use disorder; or any history of bipolar disorder, schizophrenia, schizoaffective disorder or other psychotic disorder
17. History of suicide attempt or other suicidal behavior in the previous two years.
18. Any anticipated need for surgery that might confound results or interfere with the patient's ability to comply with the protocol
19. Known allergies to hemp seeds, medical cannabis, sunflower lecithin or polysorbate
20. Current enrollment in any other research or clinical trial

Primary outcomes:
measure: Patient Global Impression of Change (PGIC)
timeFrame: Change in PGIC from beginning to end of treatment at 30 days
measure: Total Symptom Score (TSS)
timeFrame: Change in TSS from beginning to end of treatment at 30 days
Secondary outcomes:
measure: Insomnia Severity Index
timeFrame: Univariate time series analysis of change/trend of weekly responses over 30 days
measure: Harvard Flourishing Index (HFI)
timeFrame: Univariate time series analysis of change/trend of weekly responses over 30 days
measure: DANA Brain Vital
timeFrame: Univariate time series analysis of change/trend of weekly cognitive efficiency over 30 days
measure: Hours of Upright Activity
timeFrame: Univariate time series analysis of change/trend of daily responses over 30 days
measure: Daily Steps
timeFrame: Univariate time series analysis of change/trend of daily steps over 30 days
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: Bateman Horne Center
state: Utah
Study officials:
affiliation: Chief Medical Officer
name: Lucinda Bateman, MD
role: PRINCIPAL_INVESTIGATOR
References: