Growth Hormone Improves Sensory Function in Complete Spinal Injury

Becky McCall

May 24, 2017

LISBON, Portugal — Six months of treatment with growth hormone has improved sensory function in patients with spinal-cord injury and concomitant growth-hormone deficiency, according to the first such trial of this approach.

"Changes in sensory quantification (electrical perception threshold) of up to five levels below the site of spinal injury were observed," reported Gulliem Cuatrecasas, MD, PhD, an endocrinologist from Hospital Quiron-Teknon, Barcelona, Spain, who presented the work here at the European Congress of Endocrinology (ECE) 2017.

"This study looked at complete lesions, which are the severest form of spinal lesion, so we didn't really expect to find any changes," he stressed.

Although these findings seem quite remarkable, it's important that they are interpreted cautiously, "because it is not a solution for spinal-injury lesions. These patients do not walk again," he stressed.

But they may significantly affect quality of life.

With these changes of up to five levels of improvement in sensation, "they may feel [the fact] that they are in a wheelchair, or they may feel a burning sensation or similar," which may, for example, help to avoid pressure ulcers from wheelchair use.

And "autonomic nervous system processes also improved with less need for catheterization of the bladder after treatment with growth hormone," Dr Cuatrecasas noted.

There was significant improvement in the Spinal Cord Injury Independence Measure (SCIM) III score — which assessed self-care, respiration, and sphincter control — at 55.6 points vs 74 (= .05) at 3 months, and 55.4 vs 73.5 at 6 months in the growth-hormone–treated group compared with placebo.

Commenting on the work, Gemma Sesmilo, MD, an endocrinologist at University Hospital Dexeus, Barcelona, Spain, urged caution but nevertheless said, "It is encouraging to have a small pilot study showing neuronal improvement in patients with spinal-cord injury. Further studies with higher number of patients and longer duration [of therapy] are needed."

First Trial of Growth Hormone in Complete Spinal Injury

Growth-hormone deficiency is the most common anterior pituitary abnormality that occurs after traumatic brain injury, estimated to affect approximately 20% of patients.

And in patients with compete spinal injury, around 80% of those affected are deficient in growth hormone, for reasons that are not clear.

In an interview with Medscape Medical News, Dr Cuatrecasas said that few trials have investigated how this situation affects the patient's recovery.

"No specific studies have been done, prior to this one, of the use of growth hormone as treatment in complete spinal cord injuries, but previous work has been conducted in traumatic brain injury."

He stressed that the levels of growth hormone are much lower after spinal injury than following traumatic brain injury.

With animal models providing support for the concept, Dr Cuatrecasas, along with researchers at the Guttmann Institute, a neurorehabilitation hospital in Barcelona, set out to investigate the use of growth hormone in this patient population.

The double-blind, placebo-controlled, randomized controlled trial screened a total of 18 patients with complete cervicodorsal section of the spinal cord (ASIA-A).

In total, 13 patients showed growth-hormone deficiency using the glucagon test, seven of whom had growth-hormone levels of <3 ng/mL. To ensure patients were homogeneous, only those demonstrating growth-hormone deficiency were included. Of the patients, 11 were male; patients were 36 years old, on average, and 16 to 20 months from the time of injury.

Patients received subcutaneous injections of growth hormone somatropin (Nutropin, Genentech) at 0.0125 mg/kg on 6 days/week, or placebo. In addition, the patients received intensive physical therapy for 2 hours per day for 6 months. Both groups were similar in age, body mass index, and waist circumference.

Those in the treatment group (n = 7) had peak growth hormone levels of 1.8 ng/mL prior to randomization while those in the placebo group (n = 5) had levels of 5.3 ng/mL. One patient was lost to follow-up

Quantitative sensory tests were performed and the Neuropathic Pain Scale was assessed at 3 and 6 months.

The sensory test was specially designed to detect subclinical intraindividual differences, said Dr Cuatrecasas.

The test showed that patients in the growth-hormone group "regained far more feeling below the site of spinal injury after 6 months of treatment compared with the placebo group," reported Dr Cuatrecasas.

This was demonstrated by a significant improvement in the electrical perception threshold from the first up to the fifth metamera (transverse segments of the spinal cord from which two bundles of nerve fibrils attach) below the injury site. This was observed on both sides of the body.

No correlations were found with insulinlike growth factor 1 (IGF1), nor were any growth-hormone–related adverse events reported.

Repairing Damaged Nerves: Time for a Rethink?

The challenge now is to explain these findings, remarked Dr Cuatrecasas.

"We learned in medical school that once an axon is broken there is no recovery, but now this is no longer true.

"It is untrue that nerve injuries cannot be repaired; this needs to be reconsidered. We need to start understanding the connections between neuroplasticity and exercise–derived plasticity.

"Growth hormone is probably much more important than we think — we don't really know the full impact," he explained.

Future work might look at acute injury with different treatment regimens.

"These patients were recruited after at least 12 months of injury at which point no spontaneous changes are expected, but it would be interesting to discover what actually happens in acute lesions and with greater duration and higher dosage [of growth hormone]. These questions need to be answered."

Dr Sesmilo said growth hormone as well as IGF-1 have been related to neuroregeneration in preclinical and clinical models of neuronal damage, including in traumatic brain injury, Alzheimer's disease, and radiation injury.

And "this human study seems to confirm previous observations in rodent models of acute spinal injury; however, like other drugs tested in models of neuronal damage, this is a very small study of limited duration," she cautioned.

She also pointed out that the glucagon test used in the study to determine growth-hormone deficiency "could have overestimated the rate of complete spinal injury." And data on possible traumatic brain injury (concomitant with the spinal injury) in these patients were "not provided," she said.

The work was partly financed by Ipsen Pharma. Drs Cuatrecasas and Sesmilo have declared no relevant financial relationships.

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European Congress of Endocrinology 2017. May 23, 2017. Lisbon, Portugal. Abstract 12.3

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