Effectiveness of Cannabinoids on Appetite in Scleroderma

Study Overview
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Brief Summary
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The cannabinoid has benefits in many aspects but the evidence of the effect of cannabinoids in humans with SSc is limited. We, therefore, would like to investigate the efficacy of cannabinoids on the appetite, sleep efficiency, quality of life, pain, and critical cytokine level in SSc compared with placebo in SSc patients and the adverse events associated with cannabinoids in those patients.

Detailed Description
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Systemic sclerosis (SSc) is a connective tissue disease for which skin tightness is the hallmark. The disease is classified into 2 major subsets: limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous systemic sclerosis (dcSSc) depending on the extent of skin tightness. Not only the skin tightness but also the internal organs such as the musculoskeletal, kidneys, lungs, heart, and intestines can be involved and associated with a poor outcome. Malnutrition and/or weight loss is a complications in SSc. The complication is possibly related to gastrointestinal involvement, inflammation, immunosuppressant agents, or mood disturbance which can affect the food appetite or eating behavior. As well as sleep quality, sleep disturbance has been reported in SSc patients and the associated factor of sleep disturbance in those patients was gastrointestinal involvement, particularly gastroesophageal reflux disease, the severity of pain, and depressed mood. The cannabinoid is an agent which affects appetite, pain, and sleep quality as mentioned above, hence it would improve the appetite, get a high sleep quality and reduce pain associated with musculoskeletal involvement in SSc patients. Although cannabinoid has benefit in many aspects, they also resulted in serious adverse events after cannabinoid inhalation, including ischemic stroke related to vasospasm of the cerebral vessel, high cardiac output, cardiac arrhythmias, blood pressure fluctuation, and respiratory tract infection. Acute toxicity has been reported and depended on unit dose, tolerance, and route of cannabinoid use. Cannabis also influenced brain function including memory, and cognitive function, and expanded the risk for psychosis in those who had prolonged use. The symptoms of central nervous system (CNS) toxicity include euphoria, panic, agitation, mood alterations, alteration of perception, loss of social inhibition, muscle incoordination, myoclonic jerking, ataxia, slurred speech, and risk of the suicidal idea. In addition, prolonged high doses of cannabis use can lead to the development of cannabinoid hyperemesis syndrome caused by cyclic hyperemesis, finally resulting in electrolyte disturbances and impaired kidney function. Because the evidence of the effect of cannabinoids in humans with SSc is limited. We, therefore, would like to investigate the efficacy of cannabinoids on the appetite, sleep efficiency, quality of life, pain, and key cytokine level in SSc compared with placebo in SScpatientst and the adverse events associated with cannabinoids in those patients.

Official Title
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Effectiveness of Cannabinoid on Appetite, Sleep Quality, Quality of Life, Joint Pain, and Cytokine Level in Systemic Sclerosis Patients: a Randomized Placebo-controlled Trial

Conditions
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Systemic Sclerosis, Malnutrition, Loss of Appetite

Intervention / Treatment
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* Drug: CBD oil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: SSc patients aged between 18 and 65 years Diagnosed according to ACR/EULAR 2013 classification criteria Having anorexia or malnutrition status Must not receive steroid equivalent to prednisolone dose more than 10 mg/d Must receive a stable dose of steroid, immunosuppressant, and/or vitamin or its supplement within 2 weeks before enrollment Must stop anxiolytics, hypnotics, or sleeping pills at least 2 weeks before enrollment Understand and able to read and write the Thai language Exclusion Criteria: Overlap with other connective tissue diseases Pregnancy or lactation Bedridden and confined to no self-care Evidence of active malignant disease Present uncontrolled or severe medical problems including diabetes mellitus, asthma, angina, cardiovascular, thyroid, hepatic, or renal diseases (Cr>1.4 mg/dl) Present active infection that needs systemic antibiotic Previous allergy to cannabinoid or their derivatives Concomitant illegal drug used (amphetamine or its derivative, cocaine) History of the previous cannabinoid using or concomitant any herbal included cannabinoid used On-going anxiolytics, hypnotics, or sleeping pills used In a period that needs immunosuppressant dose adjustment Having active SSc that needs closed monitoring for disease progression (pulmonary hypertension, proteinuria, microscopic hematuria, digital gangrene, and progressive interstitial lung disease) Having unstable cardiopulmonary disease (angina, peripheral vascular disease, cerebrovascular disease, and arrhythmia) and risk of cardiovascular disease Having a history of schizophrenia, concurrent active mood disorder, or anxiety disorders Receiving the following medications that cause drug interaction with cannabinoids: fluoroquinolone, rifampicin, fluoxetine, warfarin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: cannabinoid versus placebo
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cannabinoid<br>Cannabinoid in form of cannabis 2.7 mg THC 2.5 mg twice daily (1 droplet twice daily; 0.73 mg THC and 0.81 mg CBD/drop, 1.46 mg THC and 1.62 CBD/day) for 1 week then titrate up to 2 droplets twice daily if tolerated (2.92 mg THC and 3.24 CBD per day) and continue the treatment until the end of the study | Drug: CBD oil<br>* The subjects will receive cannabis 2.7 mg THC 2.5 mg CBD twice daily (1 droplet twice daily; 0.73 mg THC and 0.81 mg CBD/drop, 1.46 mg THC and 1.62 CBD/day) for 1 week then titrate up to 2 droplets twice daily if tolerated (2.92 mg THC and 3.24 CBD per day) and continue the treatment until the end of the study.<br>|
| Placebo Comparator: placeba<br>Placebo 1 droplet twice daily for 1 week then titrate up to 2 droplets twice daily if tolerated and continue the treatment until the end of the study | Drug: Placebo<br>* The subjects will receive 1 droplet of placebo twice daily then titrate up to 2 droplets twice daily if tolerated and continue the treatment until the end of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changing of appetite | 50% increase of appetite evaluated by a visual analogue scale (VAS) from 0-100* compared to baseline and a comparison between the treatment group and placebo group *a higher score, a more appetite | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changing of serum transferrin level | The mean difference of serum transferrin level compare to baseline and a comparison between the treatment group and placebo group | 4 weeks | 
| An adverse event | An adverse event | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cannabinoid, appetite, quality of life, systemic sclerosis, scleroderma, clinical trial