New CRPS Treatments

The Walk to Conquer CRPS has been raising funds for new CRPS Treatment Research projects since 2018! We will share all information as it becomes available.

r(TMS):

Repetitive Transcranial Magnetic Stimulation research project at McMaster University. 

About GBM-5 Research:

From Dr. Blaise:

"Complex regional pain syndrome (CRPS) is one of the most challenging pain conditions in medicine and is ranked as the most painful form of chronic pain that exists today by the McGill Pain Index. CRPS results in loss of physical function and can lead to significant and sometimes permanent disability. It is classified as a rare disorder by the US FDA and is associated with little agreement regarding aetiology, symptoms, clinical presentation, diagnosis and treatment. In most cases, CRPS occurs after an illness or injury that did not directly damage the nerves in the affected area (Type I, 90% of cases). In other cases, it occurs after a specific nerve injury (Type II).

Both types of CRPS demonstrate continuing pain, allodynia, or hyperalgesia that is usually disproportionate to the inciting event. At some point during the syndrome's development, both types show evidence of oedema, changes in skin blood flow, or abnormal sudomotor activity in the painful region. Intensity and duration are variable, and the course of the disease seems to be unpredictable between various subjects. Study of the disease has indicated that one single mechanism cannot account for all of the changes seen in subjects with CRPS and, consequently, a single ingredient medication is unlikely to be effective in this patient population.

Despite the severe pain and disability associated with CRPS, the lack of understanding of the pathophysiological mechanisms supporting this enigmatic condition prevents the rational design of new therapies. No one knows the exact cause of CRPS, and there are no Health Canada or FDA-approved treatments for subjects with CRPS. Therefore, there is a clear demand for effective treatment options to address this important unmet medical need.

Rationale:

Prolonged severe pain that may be constant is typically the leading symptom of CRPS and is often associated with limb dysfunction and psychological distress. For those in whom pain persists, psychological symptoms (anxiety, depression) and loss of sleep are also likely to develop.

Given the heterogeneous nature of CRPS, an optimal therapy with a

Protocol MEDNC-001 GBM-5 Open-label Efficacy & Safety in CRPS Patients

Final v1.0 (16-oct-2019) CONFIDENTIAL Page 12 of 69

single ingredient seems unlikely; therefore, a mechanism-directed approach to treatment of CRPS appears preferable.

After several years of research, the team at the Montreal Pain Clinic successfully formulated a combination product (namely GBM-5) which might address some underlying mechanisms thought to be involved in the pathophysiology of CRPS, such as neurogenic inflammation, sympathetic dysfunction, etc.. This combination solution is a fixed multimodal formulation for intrathecal (IT)/epidural injection, or intranasal administration, and is clearly differentiated from other strong analgesics by its unique combined synergistic mechanism of action.

Using multiple regional injections of low dose GBM-5 (a mixture of an opioid, a Na+ channel blocker, an alpha2-receptor agonist, an opioid mu or delta receptor competitive antagonist, and an anaesthetic) in patients with medium-term and long-standing CRPS pain (duration of more than 6 months) which was not adequately controlled by currently available therapies, promising clinical results showed that: 1) pain relief was rapid and substantial; 2) a good safety profile was demonstrated; and 3) patients’ quality of life (cognitive function and mood) greatly improved. Recently, it was observed that the pain reduction lasted longer when 1.0 mL of GBM-5 nasal solution was added or used alone, and the pain relief was enhanced with compounded topical cream applied to affected areas.

Further study in more patients is warranted to confirm the efficacy of GBM-5/GBC-01.

As the clinical outcome has been shown to vary between subjects, the proposed trial protocol is tailored to treat the needs of patients individually. The primary objective is to establish the efficacy (dose/number of doses) of GBM-5/GBC-01 for reducing pain and/or opioid use, and the secondary objectives are to preserve or restore function, enable patients to manage their condition and improve their quality of life.

Objectives:

The objectives of this study are:

Primary

• To establish the efficacy of a combination of nasal spray solution and topical cream of GBM-5/GBC-01, in reducing persistent pain and/or opioid use in CRPS patients.

• To assess the safety of GBM-5 in CRPS patients.

Secondary 

To assess improvements in the patients’ quality of life (cognitive function, mood, depression, etc.). 

Exploratory 

To assess any change in disease severity by comparing the CRPS severity score (CSS) at screening with that of the end of study. 

To assess the weekly change in patient-reported pain intensity versus dose, number of treatment cycles, and disease duration "