Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response. Clinical Investigation of Duchenne Dystrophy Group

A randomized, controlled trial of daily prednisone was conducted in 99 boys (aged 5 to 15 years) with Duchenne dystrophy to define the time course of improvement and the dose response to treatment. Prednisone at 0.3 mg/kg (n = 33), prednisone at 0.75 mg/kg (n = 34), and placebo (n = 32) were administered for 6 months. Patients were examined using manual muscle and myometry testing, timed functional testing, pulmonary function testing, and laboratory measurements at 10 days, 1 month, 2 months, 3 months, and 6 months of treatment. Boys treated with prednisone had stronger average muscle strength scores, than did boys treated with placebo as early as 10 days after starting therapy. At the 3-month visit, the boys in the group given 0.75 mg/kg of prednisone were significantly stronger than those in the group given 0.3 mg/kg of prednisone, indicating a dose response. At 6 months, significant side effects occurred in the group treated with 0.75 mg/kg of prednisone, including weight gain, cushingoid appearance, and excessive hari growth. Only weight gain was observed in the group taking prednisone at a dose of 0.3 mg/kg. Importantly, no side effects were evident at 10 days or 1 month of treatment, despite improvement in muscle strength and function. We conclude that prednisone produces a rapid increase in muscle strength in patients with Duchenne dystrophy and that this improvement is maximal at a prednisone dosage of 0.75 mg/kg or less.     

A comparison of daily and alternate-day prednisone therapy in the treatment of Duchenne muscular dystrophy

We previously reported the results of a randomized, double-blind 6-month trial of prednisone therapy in which 102 boys aged 5 to 15 years with Duchenne muscular dystrophy received daily doses of 1.5 and 0.75 mg/kg per day and were compared with those receiving placebo. The strength and function in both prednisone-treated groups improved equally and were significantly better than in the placebo group. To compare alternate-day and daily dosing of prednisone with respect to benefits and adverse side effects, the placebo group was started on alternate-day prednisone therapy, and the treatment group regimens were changed to equivalent doses of alternate-day prednisone without breaking the double-blind nature. At the end of 6 months, the group that was changed from daily to alternate-day therapy had declined in strength back to levels observed 12 months previously, at the start of daily therapy. The group in which alternate-day therapy was started showed a significant improvement in strength at 3 months, similar in magnitude to the response of boys treated with daily therapy. However, their strength declined significantly in the subsequent 3 months compared with boys who received daily therapy. The frequency of side effects was not significantly different for alternate-day therapy compared with daily therapy. We conclude that alternate-day prednisone therapy effectively increases strength but does not sustain the improvement to the same extent as daily therapy or mitigate side effects.     

Myoblast implantation in Duchenne muscular dystrophy: The San Francisco study

We evaluated myoblast implantation in 10 boys with Duchenne muscular dystrophy (DMD) and absent dystrophin (age 5–10 years) who were implanted with 100 million myoblasts in the anterior tibial muscle of one leg and placebo in the other. Cyclosporine (5 mg/kg/day) was administered for 7 months. Pre- and postimplantation (after 1 and 6 months) muscle biopsies were analyzed. Force generation (tetanic tension and maximum voluntary contraction) was measured monthly in a double-blind design. There was increased force generation in both legs of all boys, probably due to cyclosporine. Using the polymerase chain reaction, evidence of myoblast survival and dystrophin mRNA expression was obtained in 3 patients after 1 month and in 1 patient after 6 months. These studies suggest a salutary effect of cyclosporine upon muscular force generation in Duchenne muscular dystrophy; however, myoblast implantation was not effective in replacing clinically significant amounts of dystrophin in DMD muscle. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 469–478, 1997.     

Efficacy of prednisone for the treatment of ocular myasthenia (EPITOME): A randomized,controlled trial

Introduction: In this study we evaluated the safety, tolerability, and efficacy of prednisone in patients with ocular myasthenia gravis (OMG) concurrently treated with pyridostigmine. Methods: This investigation was a randomized, double‐blind, placebo‐controlled trial. Participants whose symptoms failed to remit on pyridostigmine were randomized to receive placebo or prednisone, initiated at 10 mg every other day, and titrated to a maximum of 40 mg/day over 16 weeks. The primary outcome measure was treatment failure. Results: Fewer subjects were randomized than the 88 planned. Of the 11 randomized, 9 completed 16 weeks of double‐blind therapy. Treatment failure incidence was 100% (95% CI 48%–100%) in the placebo group (n = 5) vs. 17% (95% CI 0%–64%) in the prednisone group, P = 0.02 (n = 6). Median time to sustained minimal manifestation status (MMS) was 14 weeks, requiring an average prednisone dose of 15 mg/day. Adverse events were infrequent and generally mild in both groups. Conclusions: A strategy of low‐dose prednisone with gradual escalation appears to be safe, well‐tolerated, and effective in treating OMG. Muscle Nerve 53: 363–369, 2016     

Mononuclear cell analysis of muscle biopsies in prednisone-treated and untreated Duchenne muscular dystrophy. CIDD Study Group

A recent double-blind, placebo-controlled trial has shown that prednisone improves strength in patients with Duchenne muscular dystrophy. To determine whether immunosuppressant effects were important in mediating this improvement, we performed immunohistochemical analyses on muscle biopsies obtained at the conclusion of the trial. We studied 33 patients: 12 from the placebo group, nine from the low-dose prednisone group (0.75 mg/kg/d), and 12 from the high-dose group (1.5 mg/kg/d). There was a significant difference in total T cells (CD2+) between the placebo group and both treatment groups. Similarly, the number of CD8+ cytotoxic/suppressor T cells was significantly decreased in both treated groups compared with placebo. The number of muscle fibers focally invaded by lymphocytes was also significantly decreased in the two treated groups compared with controls. There were no differences between the low- and high-dose groups. The numbers of B cells, natural killer cells, CD4+ cells, macrophages, and necrotic muscle fibers were not significantly different in the treated and control groups. This study suggests that prednisone may improve strength in Duchenne muscular dystrophy through primarily immunologic mechanisms involving T lymphocytes.     

Benefits of FK506 (tacrolimus) for residual, cyclosporin- and prednisone-resistant myasthenia gravis: one-year follow-up of an open-label study

Thirteen patients with myasthenia gravis, unresponsive to prednisone and cyclosporin after thymectomy, received KF506 (tacrolimus) for 12 months, at starting doses of 0.1 mg/kg per day b.i.d. and then adjusted to achieve plasma concentrations between 7 and 8 ng/mL. The doses of prednisone were progressively reduced and finally discontinued. Anti-acetylcholine antibodies and myasthenia gravis score for disease severity decreased significantly and muscular strength increased by 37%. All patients achieved pharmacological remission, 11 were asymptomatic and two had minimal weakness of eyelid closure. Tacrolimus was well tolerated and appears a suitable approach after unsuccessful treatment with conventional immunosuppressants in patients with disabling myasthenia.     

Effect of high- and low-dose dexamethasone on regeneration of minced skeletal muscle autografts in rats

Minced skeletal muscle autografts were carried out in 96 male Sprague-Dawley rats weighing 150 to 175 g. Starting the day of surgery, dexamethasone (DEX) was administered parenterally, 3 X/day, at one of the following doses: 0, 0.001, 0.01, 0.1, or 1.0 mg/kg. Separate groups received each dosage for either 7 or 21 days (N = 8 to 16 per group). On day 22, rats were killed and the immature grafts were excised and weighed. The total number of muscle cells was counted on transverse sections. Collagen, dry matter content, and total and noncollagen protein were measured. The wet weights and the total number of muscle cells for 1.0 or 0.1 mg/kg DEX grafts were less than most other groups, after treatment of either 7 or 21 days. In contrast, 0.001 mg/kg DEX for 21 days was associated with increased cell counts. For either treatment duration, collagen content was higher for 0.001 mg/kg DEX. After 21 days DEX, 0.1 and 0.01 mg/kg groups also had more collagen compared with controls. (The 1.0 mg/kg DEX grafts were not assayed for collagen due to insufficient tissue regeneration). In a subsequent trial, rats received 0.001 mg/kg DEX (N = 14) or vehicle control (N = 11) for 21 days. On day 60, the rats were killed and the grafts, now near maturity, were again analyzed for total myofiber number and collagen content, neither of which was significantly different from controls. In summary, DEX in pharmacologic doses was associated with inhibition of muscle graft regeneration if administered for 7 or 21 days. There was evidence that DEX at 100 to 1000 X lower concentrations caused transient increases in the number of proliferating muscle cells and the collagen concentration.     

Cigarette smoke and nicotine protect dopaminergic neurons against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Parkinsonian toxin

Epidemiological studies have found a negative association between cigarette smoking and Parkinson's disease (PD). In order to analyze the putative neuroprotective effect of cigarette smoke and nicotine, one of its major constituents, we examined their effects in an animal model of PD provoked by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. Two groups of mice were chronically exposed to cigarette smoke (a low exposure subgroup and a high exposure subgroup; 5 exposures per day at 2-h intervals), two other groups received nicotine treatment (two doses tested 0.2 and 2 mg/kg, 5 injections i.p. per day at 2-h intervals) and one group placebo. On day 8 after the beginning of the treatment, 4 injections of MPTP hydrochloride (15 mg/kg, i.p., at 2-h intervals) or saline were administered to these animals. Nicotine and cotinine plasmatic concentration was quantified by the HPLC method, and degeneration of the nigrostriatal system was assessed by tyrosine hydroxylase (TH) immunohistochemistry. The loss of dopaminergic neurons induced by MPTP in the substantia nigra was significantly less severe in the chronic nicotine treatment groups (at 0.2 and 2 mg/kg) and the low exposure to cigarette smoke group than in the high exposure to cigarette smoke subgroup and the placebo treated subgroup. In contrast, no preservation of TH immunostaining of nerve terminals was observed in the striatum in any group. This suggests that nicotine and low exposure to cigarette smoke may have a neuroprotective effect on the dopaminergic nigrostriatal system by an as yet unknown mechanism.     

Opioid neurotoxicity: comparison of morphine and tramadol in an experimental rat model

Histopathologic changes in rat brain due to chronic use of morphine and/or tramadol in progressively increased doses were investigated in this study. Thirty male Wistar rats (180-220 g) were included and divided into three groups. Normal saline (1 ml/kg) was given intraperitoneally as placebo in the control group (n = 10). Morphine group (n = 10) received morphine intraperitoneally at a dose of 4 mg/kg/day for the first 10 days, 8 mg/kg/day between 11-20 days, and 12 mg/kg/day between 21-30 days. The tramadol group (n = 10) received the drug intraperitoneally at doses of 20, 40, and 80 mg/kg/day in the first, second, and the third 10 days of the study, respectively. All rats were decapitated on the 30th day and the brain was removed intact for histology. The presence and the number of red neurons, which are a histologic marker of apoptosis, were investigated in the parietal, frontal, temporal, occipital, entorhinal, pyriform, and hippocampal CA1, CA2, CA3 regions. Red neurons were found in morphine and tramadol groups but not in the control group. The total number of red neurons was not different in morphine and tramadol groups, but the numbers of red neurons were significantly higher in the temporal and occipital regions in tramadol group as compared with the morphine group (p < .05). In conclusion, chronic use of morphine and/or tramadol in increasing doses is found to cause red neuron degeneration in the rat brain, which probably contributes to cerebral dysfunction. These findings should be taken into consideration when chrome use of opioids is indicated.     

Fenfluramine in the treatment of Dravet syndrome: Results of a third randomized,placebo-controlled clinical trial

Objective

This study was undertaken to assess the safety and efficacy of fenfluramine in the treatment of convulsive seizures in patients with Dravet syndrome.

Methods

This multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial enrolled patients with Dravet syndrome, aged 2–18 years with poorly controlled convulsive seizures, provided they were not also receiving stiripentol. Eligible patients who had ≥6 convulsive seizures during the 6-week baseline period were randomized to placebo, fenfluramine .2 mg/kg/day, or fenfluramine .7 mg/kg/day (1:1:1 ratio) administered orally (maximum dose = 26 mg/day). Doses were titrated over 2 weeks and maintained for an additional 12 weeks. The primary endpoint was a comparison of the monthly convulsive seizure frequency (MCSF) during baseline and during the combined titration–maintenance period in patients given fenfluramine .7 mg/kg/day versus patients given placebo.

Results

A total of 169 patients were screened, and 143 were randomized to treatment. Mean age was 9.3 ± 4.7 years (±SD), 51% were male, and median baseline MCSF in the three groups ranged 12.7–18.0 per 28 days. Patients treated with fenfluramine .7 mg/kg/day demonstrated a 64.8% (95% confidence interval = 51.8%–74.2%) greater reduction in MCSF compared with placebo (p < .0001). Following fenfluramine .7 mg/kg/day, 72.9% of patients had a ≥50% reduction in MCSF compared with 6.3% in the placebo group (p < .0001). The median longest seizure-free interval was 30 days in the fenfluramine .7 mg/kg/day group compared with 10 days in the placebo group (p < .0001). The most common adverse events (>15% in any group) were decreased appetite, somnolence, pyrexia, and decreased blood glucose. All occurred in higher frequency in fenfluramine groups than placebo. No evidence of valvular heart disease or pulmonary artery hypertension was detected.

Significance

The results of this third phase 3 clinical trial provide further evidence of the magnitude and durability of the antiseizure response of fenfluramine in children with Dravet syndrome.     

Efficacy and tolerability of 1000-4000 mg per day of levetiracetam as add-on therapy in patients with refractory epilepsy

The aim of this study was to determine the efficacy and tolerability of 1000-4000 mg/day of levetiracetam (LEV, Keppra) as add-on treatment for refractory epilepsy. This was a dose-escalation study of 29 patients with refractory epilepsy. Patients received placebo for 4 weeks (baseline) followed by levetiracetam 1000 and 2000 mg per day each for 2 weeks, and then 3000 and 4000 mg per day each for 4 weeks. Primary efficacy was assessed by seizure frequency (number/week). Tolerability was assessed by adverse events, laboratory parameters, clinical evaluations, and electrocardiogram. All the study periods were completed by 27 of the 29 patients. A substantially lower median seizure frequency was observed at all levetiracetam dosing periods (1000 mg per day, 1.0 seizures per week; 2000 mg per day, 1.5 seizures per week; 3000 mg per day, 1.0 seizures per week; 4000 mg per day, 0.75 seizures per week) compared with the placebo treatment (2.06 seizures per week). In addition, 22-33% of these patients were seizure free during treatment with levetiracetam compared with only 14% with placebo. Levetiracetam was well tolerated. The most common adverse events were somnolence and asthenia; frequency and severity increased with increasing doses of levetiracetam. Levetiracetam in doses from 1000 to 4000 mg per day is effective. Somnolence and asthenia were more frequent with the highest dose, suggesting that 4000 mg per day may be the upper limit in some patients, although individual susceptibility to somnolence was variable.     

Clinical efficacy of istradefylline (KW‐6002) in Parkinson's disease: A randomized,controlled study

The objectives of this study were to evaluate the efficacy of istradefylline at an oral dose of 20 mg or 40 mg once daily for 12 weeks in Parkinson's disease (PD) patients with motor complications on levodopa therapy based on the change in the daily OFF time compared with placebo and to assess the safety at these doses. A total of 363 subjects were randomly assigned to receive 20 mg/day istradefylline (n = 119), 40 mg/day istradefylline (n = 125), or placebo (n = 119). The primary outcome variable was the change from baseline at endpoint in daily OFF time based on patients' ON/OFF diaries. At endpoint, the daily OFF time reduced from baseline by 1.31 hours for 20 mg/day istradefylline (P = 0.013 as compared to the placebo), 1.58 hours for 40 mg/day istradefylline (P < 0.001), and 0.66 hours for placebo; istradefylline significantly reduced the daily OFF time compared with placebo. The UPDRS Part III subscale score (ON state) reduced by 5.7 at endpoint in both istradefylline groups and 3.7 in the placebo group (P = 0.006 for 20 mg/day and P = 0.006 for 40 mg/day group as compared with placebo). The most commonly reported drug‐related treatment emergent adverse event (TEAE) was dyskinesia, which occurred in 2.5% (3/119) of subjects receiving placebo, 8.5% (10/118) receiving 20 mg/day istradefylline, and 6.4% (8/125) receiving 40 mg/day istradefylline. We conclude that istradefylline at 20 mg and 40 mg once daily is effective in relieving wearing‐off fluctuations of PD patients. In addition, istradefylline was well tolerated at both doses. © 2010 Movement Disorder Society     

A double-blind, placebo-controlled, randomized, multi-center study of pramipexole in advanced Parkinson's disease

Pramipexole (SND 919), a potent non-ergot dopamine agonist, or placebo, was administered to 69 patients with advanced Parkinson's disease (33 received placebo, 36 received pramipexole) in a double-blind, randomized, multi-center study in which individually optimized doses of l -dopa plus a dopa decarboxylase inhibitor were associated with dyskinesia, "on–off" fluctuation, dystonia, akinesia, or end-of-dose deterioration. Study medication was titrated over 7 weeks to the maximal tolerated dose or to the maximal dose allowed by the study (5 mg/day in four divided doses). Dosing was maintained for 4 weeks and then tapered during the final week. Total score on the Unified Parkinson's Disease Rating Scale (UPDRS) for the intent-to-treat population was significantly improved in the pramipexole-treated group compared with the placebo-treated group (16.9 ± 14.9 vs 9.0 ± 16.1; p = 0.0184). By the end of maintenance, the mean reduction in l -dopa requirement was −150.7 mg for pramipexole-treated patients compared to −10.6 for placebo-treated patients. The most common adverse events (> 10%) were dizziness, insomnia, nausea, and postural hypotension. Aggravated parkinsonism occurred only after withdrawal of the study medication. Treatment with pramipexole in doses up to 5 mg/day was safe and well tolerated by patients with advanced Parkinson's disease.     

Altered phosphorylation of rat neuronal cytoskeletal proteins in acrylamide induced neuropathy

The activity of protein kinase has been assayed in neurofilament preparations from spinal cords of rats treated with acrylamide. Animals received 50 mg/kg, i.p., of acrylamide per day for a total of 5 or 10 days; these doses produce mild and marked symptoms of neurological damage, respectively. Incorporation of phosphate into proteins was determined using [gamma-32P]ATP followed by SDS-PAGE. Total phosphorylation of neurofilament preparations was significantly increased only in the animals treated with the 500 mg/kg cumulative dose of acrylamide. Phosphorylation of the 200 and 155 kdalton subunits of the neurofilaments was increased by 20-40% in the acrylamide treated groups. The phosphorylation of the 70 kdalton neurofilament subunit was unchanged in the 250 mg/kg group and was significantly decreased in the 500 mg/kg group. Phosphorylation of other protein bands was not altered. These results suggest a mechanism by which acrylamide might produce axonal neurofilamentous accumulations.     

Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling

OBJECTIVE: Pathological gambling is a disabling disorder experienced by approximately 1%-2% of adults and for which there are few empirically validated treatments. The authors examined the efficacy and tolerability of the opioid antagonist nalmefene in the treatment of adults with pathological gambling. METHOD: A 16-week, randomized, dose-ranging, double-blind, placebo-controlled trial was conducted at 15 outpatient treatment centers across the United States between March 2002 and April 2003. Two hundred seven persons with DSM-IV pathological gambling were randomly assigned to receive nalmefene (25 mg/day, 50 mg/day, or 100 mg/day) or placebo. Scores on the primary outcome measure (Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling) were analyzed by using a linear mixed-effects model. RESULTS: Estimated regression coefficients showed that the 25 mg/day and 50 mg/day nalmefene groups had significantly different scores on the Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling, compared to the placebo group. A total of 59.2% of the subjects who received 25 mg/day of nalmefene were rated as "much improved" or "very much improved" at the last evaluation, compared to 34.0% of those who received placebo. Adverse experiences included nausea, dizziness, and insomnia. CONCLUSIONS: Subjects who received nalmefene had a statistically significant reduction in severity of pathological gambling. Low-dose nalmefene (25 mg/day) appeared efficacious and was associated with few adverse events. Higher doses (50 mg/day and 100 mg/day) resulted in intolerable side effects.     

Randomized double-blind study with prednisone in Sydenham's chorea

In this randomized, double-blind, parallel study of a group of 22 children and teenagers, prednisone efficacy in acute Sydenham's chorea was assessed. Use of prednisone (2 mg/kg/day during 4 weeks, followed by a gradual discontinuation) in the 22 patients and in a placebo group (n = 15) was evaluated by a chorea intensity score based on presence, distribution, and interference of choreic movement on daily activities. Each patient was evaluated by the same pediatric neurologist weekly during the first month, followed by evaluation on weeks 8 and 12, with further evaluations as necessary if choreic movements persisted. Although initial chorea intensity was similar in both groups, a significant difference was observed after 1 week of medication (P < 0.001) with a larger reduction in the prednisone group, that continued until the end of the study. Percentage decrease in chorea intensity scale score also was persistently and significantly (P < 0.001) greater in the prednisone group. Chorea complete remission time with prednisone (mean 54.3 days) was significantly shorter (P < 0.001) when compared with the placebo group (mean 119.9 days). Seven patients presented recurrences, with no difference between groups (13.6% and 26.7% in the prednisone and placebo groups, respectively). Severe adverse events to prednisone were not observed.     

Risperidone Dosing in Children and Adolescents with Autistic Disorder: A Double-Blind, Placebo-Controlled Study

Efficacy and safety of 2 risperidone doses were evaluated in children and adolescents with autism. Patients (N = 96; 5–17 years), received risperidone (low-dose: 0.125 mg/day [20 to <45 kg], 0.175 mg/day [>45 kg] or high-dose: 1.25 mg/day [20 to <45 kg], 1.75 mg/day [>45 kg]) or placebo. Mean baseline (range 27–29) to endpoint change in Aberrant Behavior Checklist-Irritability (primary endpoint) was significantly greater in the high-dose—(?12.4 [6.5]; p < 0.001), but not low-dose (?7.4 [8.1]; p = 0.164) group, versus placebo (?3.5 [10.7]). Clinical Global Impressions-Severity and Children’s Yale-Brown Obsessive Compulsive Scale scores improved significantly only in the high-dose group, consistent with ABC-I results. Somnolence, sedation and increased appetite occurred more frequently in high-versus low-dose groups. Overall, increased appetite occurred most frequently.     

Developmental effects of +/-3,4-methylenedioxymethamphetamine on spatial versus path integration learning: effects of dose distribution

We previously demonstrated that postnatal day 11-20 +/-3,4-methylenedioxymethamphetamine (MDMA) exposure reduces locomotor activity and impairs path integration and spatial learning independent of the effects on activity. The effects were seen when the drug was administered twice per day, but the optimal dosing regimen is unknown. We tested whether the same total daily dose of MDMA administered in different patterns would equally affect later behavior. A split-litter design (15 litters) was used with one male/female pair per litter receiving one of four treatment regimens. All offspring received four injections per day on P11-20 as follows: 40 x 1 (40 mg/kg MDMA x 1 + saline x 3), 20 x 2 (20 mg/kg MDMA x 2 + saline x 2), 10 x 4 (10 mg/kg MDMA x 4), or Saline (saline x 4). Doses were spaced 2 h apart. Group 40 x 1 received MDMA as the first daily dose followed by three saline doses; group 20 x 2 received MDMA as the first and last dose and saline for the middle two doses; group 10 x 4 received MDMA for all four doses; and the saline group received saline for all four doses. Regardless of dose schedule, all groups treated with MDMA exhibited reduced locomotor activity. No MDMA effects were found on swimming ability in a straight channel. Modest MDMA effects were found on Barnes maze performance. The major findings were that the 40 x 1 and 20 x 2 MDMA groups showed impaired Cincinnati multiple T-water-maze learning and the 10 x 4 and 20 x 2 MDMA groups showed impaired Morris water maze learning. The results suggest that MDMA dose distribution has a long-term differential effect on different types of learning. Dose distribution warrants greater attention in the design of developmental drug studies along with the standard considerations of dose and age.     

Changes in skeletal muscle histology and metabolism in patients undergoing exercise deconditioning: Effect of propionyl-L-carnitine

To define the skeletal muscle abnormalities in patients undergoing exercise deconditioning and evaluate the metabolic effect of propionyl-L-carnitine (PLC), muscle biopsies were obtained from 28 patients with effort angina and 31 control subjects. Coronary artery disease patients received either placebo (n = 12), PLC (1.5 g IV followed by infusion of 1 mg/kg/min for 30 min, n = 10), or L-carnitine (1 g IV followed by infusion of 0.65 mg/kg/min for 30 min, n = 6) for 2 days. Exercise deconditioned patients treated with placebo showed normal muscle content of total carnitine and glycogen, and decrease in percentage of type 1 fibers (P < 0.01) and in the activity of citrate synthase (P < 0.05), succinate dehydrogenase (P < 0.05), and cytochrome oxidase (P < 0.05), as compared to controls. Both PLC and L-carnitine did not modify muscle fiber composition or enzyme activities, but significantly increased muscle levels of total carnitine by 42% and 31%, respectively (P < 0.05). Moreover, PLC significantly increased glycogen muscle content (P < 0.01), while the equimolar dose of L-carnitine did not. This effect, probably due to the anaplerotic activity of the propionic group of PLC, suggests that this drug may be effective in improving energy metabolism of muscles with impaired oxidative capacity. © John Wiley & Sons, Inc. Muscle Nerve 20: 1115–1120, 1997