Cannabis for Spasticity in Multiple Sclerosis

NCT00682929 | Terminated Phase 1 Results DMC

• 2 other identifiers: 251429MS Society Award # RG 3781-A-1
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to learn if the use of inhaled cannabis (marijuana) and oral cannabinoid (dronabinol, Marinol or THC, which is an active ingredient of marijuana) is safe and effective in reducing the symptoms of spasticity and tremor in patients with secondary-progressive or primary progressive multiple sclerosis.

Conditions

Multiple Sclerosis

Keywords

cannabis; marijuana; Multiple Sclerosis; spasticity

Outcome Measures

Primary Outcomes (4)

• Change From Week 0 to Week 3 in the Rate of Torque Increase, Flexion

  A modified servo-controlled torque motor system (Lido WorkSet II) was designed for this study to analyze the resistance to passive movement of the knee. It determines the amount of torque required to move the knee joint (without voluntary resistance) at high velocities (up to 200 degrees per second) and at slow velocities (as low as 10 degrees per second). The slow displacement torque is a measure of the passive resistance to movement (from the connective tissue and the non-contracting muscle) and the rapid displacement torques are the sum of the passive and active (involuntary) resistance. The active (involuntary) resistance is the result of the stretch reflex and correlates well with the clinical assessment of spasticity. The change was calculated by taking the value at Week 3 and subtracting the value at Week 0. A negative result indicates a decrease in the torque measured and correlates to a decrease in spasticity and a better outcome.

  Week 0, Week 3

• Change From Week 0 to Week 3 in the Rate of Torque Increase, Extension

  A modified servo-controlled torque motor system (Lido WorkSet II) was designed for this study to analyze the resistance to passive movement of the knee. It determines the amount of torque required to move the knee joint (without voluntary resistance) at high velocities (up to 200 degrees per second) and at slow velocities (as low as 10 degrees per second). The slow displacement torque is a measure of the passive resistance to movement (from the connective tissue and the non-contracting muscle) and the rapid displacement torques are the sum of the passive and active (involuntary) resistance. The active (involuntary) resistance is the result of the stretch reflex and correlates well with the clinical assessment of spasticity. The change was calculated by taking the value at Week 3 and subtracting the value at Week 0. A negative result indicates a decrease in the torque measured and correlates to a decrease in spasticity and a better outcome.

  Week 0, Week 3

• Change From Week 0 to Week 7 in the Rate of Torque Increase, Flexion

  A modified servo-controlled torque motor system (Lido WorkSet II) was designed for this study to analyze the resistance to passive movement of the knee. It determines the amount of torque required to move the knee joint (without voluntary resistance) at high velocities (up to 200 degrees per second) and at slow velocities (as low as 10 degrees per second). The slow displacement torque is a measure of the passive resistance to movement (from the connective tissue and the non-contracting muscle) and the rapid displacement torques are the sum of the passive and active (involuntary) resistance. The active (involuntary) resistance is the result of the stretch reflex and correlates well with the clinical assessment of spasticity. The change was calculated by taking the value at Week 7 and subtracting the value at Week 0. A negative result indicates a decrease in the torque measured and correlates to a decrease in spasticity and a better outcome.

  Week 0, Week 7

• LIDO Machine Score - Rate of Torque Increase, Extension

  A modified servo-controlled torque motor system (Lido WorkSet II) was designed for this study to analyze the resistance to passive movement of the knee. It determines the amount of torque required to move the knee joint (without voluntary resistance) at high velocities (up to 200 degrees per second) and at slow velocities (as low as 10 degrees per second). The slow displacement torque is a measure of the passive resistance to movement (from the connective tissue and the non-contracting muscle) and the rapid displacement torques are the sum of the passive and active (involuntary) resistance. The active (involuntary) resistance is the result of the stretch reflex and correlates well with the clinical assessment of spasticity. The change was calculated by taking the value at Week 7 and subtracting the value at Week 0. A negative result indicates a decrease in the torque measured and correlates to a decrease in spasticity and a better outcome.

  Week 0, Week 7

Secondary Outcomes (50)

• Change From Week 0 to Week 3 in Modified Ashworth Score (MAS)

  Week 0, Week 3

• Change From Week 0 to Week 7 in Modified Ashworth Score

  Week 0, Week 7

• Change From Week 0 to Week 3 in Ambulation Index (AI) Score

  Week 0, Week 3

• Change From Week 0 to Week 7 in Ambulation Index (AI) Score

  Week 0, Week 7

• Change From Week 0 to Week 3 in 25 Foot Walk Time

  Week 0, Week 3

Study Arms (3)

1) Inhaled Cannabis

ACTIVE COMPARATOR

Inhaled cannabis is compared to oral placebo.

Drug: Inhaled Cannabis; Drug: Oral Placebo

2) Oral THC

ACTIVE COMPARATOR

Inhaled placebo is compared to oral THC.

Drug: Oral THC; Drug: Inhaled placebo

3) Placebo

PLACEBO COMPARATOR

Inhaled placebo is compared to oral placebo.

Drug: Oral Placebo; Drug: Inhaled placebo

Interventions

Inhaled Cannabis DRUG

Participants will be instructed to smoke one cannabis cigarette, daily for 7 weeks.

Also known as: Cannabis

1) Inhaled Cannabis

Oral THC DRUG

Participants will be instructed to take two 5 mg dronabinol tablets two hours prior to the inhaled medication, daily for 7 weeks.

Also known as: dronabinol

2) Oral THC

Oral Placebo DRUG

Participants will be instructed to take two placebo tablets two hours prior to the inhaled medication, daily for 7 weeks.

Also known as: placebo

1) Inhaled Cannabis; 3) Placebo

Inhaled placebo DRUG

Participants will be instructed to smoke one placebo cigarette, daily for 7 weeks.

Also known as: placebo

2) Oral THC; 3) Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of clinically definite multiple sclerosis as defined by Poser criteria
• Moderate or severe spasticity
• Age 21 or older
• Must live close to the Sacramento, CA area

You may not qualify if:

• Preexisting pulmonary conditions, including poorly controlled asthma, chronic bronchitis, emphysema, bronchiectasis, and other significant pulmonary disorders
• Preexisting cardiac conditions, including ischemic heart disease, congestive heart failure, and other significant cardiac disorders
• Inability to abstain from tobacco or marijuana smoking, or use of alcohol or sedative or hypnotic medications during the duration of the study
• Pre-existing dementia, mania, depression or schizophrenia or other poorly controlled psychiatric illness
• Past history of abuse of recreational drugs, including marijuana and alcohol in the last 12 months
• History of or currently meets DSM-IV criteria for dependence on cannabis
• Use of cannabis, marijuana, or THC in the last four weeks
• Preexisting dementia, mania, depression, or schizophrenia or other poorly controlled psychiatric illness
• Exacerbation of MS within 30 days prior to screening visit
• Current use of cyclophosphamide, mitoxantrone, or cladribine
• Arthritis, bony and soft tissue disorders interfering with spasticity measures
• Inability to provide informed consent
• Recent cannabis use of more than twice per week one month prior to study entry
• For females of child bearing potential, inability to comply with adequate contraception

Sponsors & Collaborators

• University of California, Davis: lead
• National Multiple Sclerosis Society: collaborator

Study Sites (1)

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis; Marijuana Abuse; Muscle Spasticity

Interventions

nabiximols; Dronabinol

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Limitations and Caveats

This study was terminated early due to difficulty with enrollment and logistical issues, despite the enrollment period being extended over several years. Data not analyzed due to insufficient enrollment and funds, as well as the departure of the PI.

Results Point of Contact

• Title: Janelle Butters, NP
• Organization: UC Davis Health

jbutters@ucdavis.edu

916-734-6276

Study Officials

• Michelle Apperson, MD, PhD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2008
• First Posted: May 23, 2008
• Study Start: April 14, 2004
• Primary Completion: August 17, 2011
• Study Completion: August 17, 2011
• Last Updated: May 18, 2018
• Results First Posted: May 18, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)