Evidence tables

Advice

Table 3 Bresolin et al. 1990

Study reference	Bresolin N, Doriguzzi C, Ponzetto C et al. (1990) Ubidecarenone in the treatment of mitochondrial myopathies: A multi-center double-blind trial. Journal of the Neurological Sciences 100 (1–2): 70–78
Unique identifier	Not provided
Study type	2 phase study. Phase 1 was an open-label non-comparative, before and after investigation, phase 2 was a blind comparative non-randomised investigation
Aim of the study	To evaluate the effects of treatment with co-enzyme Q10 in people with mitochondrial myopathies
Study dates	Not provided
Setting	5 centres in Italy
Number of participants	59 participants entered the open label phase and 44 completed it. The 16 participants who were selected as responders entered the comparative phase
Population	In the open label phase there were 59 participants (33 female and 26 male, age range 16 to 82 years) with mitochondrial myopathies. Of these 41 people had CPEO with proximal limb weakness, 9 people had clinical features of KSS, 6 people had mitochondrial myopathy without ophthalmoplegia and 3 people had MERRF syndrome. In the group of 16 participants who were selected for the comparative phase, 13 had CPEO with muscle weakness, 1 had MERRF syndrome, 1 had KSS and 1 had mitochondrial myopathy without CPEO
Inclusion criteria	Inclusion criteria for the comparative phase was a response to co-enzyme Q10 defined as at least a 25% reduction in post-exercise serum lactate after 6 months' treatment
Exclusion criteria	No exclusion criteria provided
Intervention(s)	Co-enzyme Q10 at a dose of 2 mg per kg daily in both the open-label and comparative phases^a
Comparator(s)	Placebo in the comparative phase
Length of follow-up	6 months in the open-label phase and 3 months in the comparative phase
Outcomes	The primary outcome was not specified. The study assessed several functional and biochemical measures including: Medical Research Council muscle scale scores^b Serum lactate levels after exercise^c
Source of funding	Details not provided
Overall risk of bias/quality assessment of double-blind phase of study (CASP RCT checklist)	Did the trial address a clearly focused issue?	No
	Was the assignment of participants to treatments randomised?	No
	Were participants, health workers and study personnel blinded?	Unclear^d
	Were the groups similar at the start of the trial?	Unclear^e
	Aside from the experimental intervention, were the groups treated equally?	Unclear^f
	Were all of the participants who entered the trial properly accounted for at its conclusion?	Yes
	How large was the treatment effect?	See tables 6 and 7
	How precise was the estimate of the treatment effect?	See tables 6 and 7
	Can the results be applied in your context? (or to the local population)	Unclear^f
	Were all clinically important outcomes considered?	Unclear^f
	Are the benefits worth the harms and costs?	See key points
Study limitations	Entry to the comparative phase of the study was contingent on a pre-determined response to the study medicine in the open-label phase The comparative phase was not randomised Insufficient information is provided to assess whether the comparative phase was single or double-blinded or if the co-enzyme Q10 and placebo groups were similar at the start of study
Comments	^aParticipants took co-enzyme Q10 for 6 months during the open-label phase of the study. Participants who entered the comparative phase then took either co-enzyme Q10 or placebo for 3 months. ^b Two neurologists completed the Medical Research Council muscle scale for different muscle groups. This was conducted at the beginning of the trial then every 2 months during the open-label phase and monthly during the comparative phase. ^cSerum lactate levels were measured at baseline and 5 and 60 minutes after standard exercise on a bicycle ergometer. This test was conducted at the beginning of the trial and then every 2 months during the open-label phase and monthly during the comparative phase. ^d Insufficient information provided in paper to assess whether this was single or double blinding. ^e The paper reports that the 2 groups in the comparative phase were balanced for clinical and biochemical parameters. However, insufficient information is provided in the paper to be able to assess this, for example there are no baseline characteristics tables. ^f Insufficient information provided in the paper to assess.
Abbreviations: CPEO, chronic progressive external ophthalmoplegia syndromes; KSS, Kearns-Sayre syndrome; MERRF, myoclonus epilepsy with ragged-red fibres; RCT, randomised controlled trial.

Table 4 Chen et al. 1997

Study reference	Chen RS, Huang CC, Chu N S (1997) Coenzyme Q10 treatment in mitochondrial encephalomyopathies. Short-term double-blind, crossover study. European neurology 37 (4): 212–18
Unique identifier	Not provided
Study type	Double-blind placebo-controlled crossover study
Aim of the study	To evaluate the effectiveness of treatment with co-enzyme Q10 in people with mitochondrial encephalomyopathies
Study dates	Not provided
Setting	1 centre in Taiwan
Number of participants	8 participants included in study, results presented for 7 participants (1 participant died from intracerebral haemorrhage)
Population	Eight participants (5 female and 3 male, age range 17 to 68 years) with mitochondrial encephalomyopathy. Four participants had MERRF, 3 had MELAS and 1 had CPEO. Disease duration ranged from 2 to 33 years
Inclusion criteria	No inclusion criteria provided
Exclusion criteria	No exclusion criteria provided
Intervention(s)	Co-enzyme Q10 at a dose of 160 mg daily for 3 months^a
Comparator(s)	Placebo for 1 month^a
Length of follow-up	3 months while taking co-enzyme Q10, 1 month while taking placebo
Outcomes	The primary outcome was not specified. Study outcomes included the following which were assessed each month: Patient assessment of fatigue^b Medical Research Council muscle scale scores^c Sustained endurance strength^d
Source of funding	Grant from the National Service Council
Overall risk of bias/quality assessment (CASP RCT checklist)	Did the trial address a clearly focused issue?	No
	Was the assignment of participants to treatments randomised?	Yes
	Were participants, health workers and study personnel blinded?	Unclear^e
	Were the groups similar at the start of the trial?	Yes
	Aside from the experimental intervention, were the groups treated equally?	Yes
	Were all of the participants who entered the trial properly accounted for at its conclusion?	Yes
	How large was the treatment effect?	See table 8
	How precise was the estimate of the treatment effect?	See table 8
	Can the results be applied in your context? (or to the local population)	Unclear^f
	Were all clinically important outcomes considered?	Unclear^f
	Are the benefits worth the harms and costs?	See key points
Study limitations	The study included only 8 participants therefore it may have been insufficiently powered to reliably detect any differences in effect between placebo and co-enzyme Q10 Several outcomes were assessed and the primary endpoint was not defined The study design may have allowed a blinded assessor to know whether a participant was on treatment or placebo. If participants were randomised to receive co-enzyme Q10 first and placebo second, there was a wash-out period of 1 month before the placebo phase started Participants included in the study had a disease duration of several years. No information was provided in the paper on current medication including nutritional supplements that participants may have been taking prior to entering study Treatment and follow-up period may have been too short to fully assess effectiveness of co-enzyme Q10
Comments	^aParticipants took co-enzyme Q10 for 3 months and placebo for 1 month. If participants were randomised to receive co-enzyme Q10 first and placebo second, there was a wash-out period of 1 month before the placebo phase started. ^b Patient assessment of fatigability after continuous exercise, usual ADL and capacity of activity in the upper and lower limbs. All scored on a 6 point scale from Grade 1 normal or no fatigue in ADL to Grade 6 severe impairment of activities of daily living and use of walking assistance or in wheelchair. ^c Two neurologists completed the Medical Research Council muscle scale for different muscle groups at enrolment to study and monthly after treatment. The muscle scale grades muscle power on a scale of 0 to 5 in relation to the maximum expected for that muscle. ^d Time taken (in seconds) to complete the following movements: raising head from bed to a 30 to 45 degree angle in the supine position, lifting legs from bed to a 30 to 45 degree angle in the supine position, stretching out arms horizontally holding a 0.5 kg weight in each hand and preforming rapid thumb tapping on a special counter for 30 seconds. ^e The study was reported to be double-blind. Information is provided on how the treatment protocol was blinded to physicians. However, blinding may have been unmasked by use of a washout period after treatment in participants initially randomised to co-enzyme Q10 but not those participants initially randomised to placebo. ^f Insufficient information provided in paper to assess.
Abbreviations: ADL, activities of daily living; CPEO, chronic progressive external ophthalmoplegia syndromes; MELAS, mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes; MERRF, myoclonus epilepsy with ragged-red fibres; RCT, randomised controlled trial.

Table 5 Glover et al. 2010

Study reference	Glover EI, Martin J, Maher A et al. (2010) A randomized trial of coenzyme Q10 in mitochondrial disorders. Muscle and Nerve 42 (5): 739–48
Unique identifier	Not provided
Study type	Randomised double-blind placebo-controlled crossover study
Aim of the study	To evaluate the effectiveness of treatment with co-enzyme Q10 in people with mitochondrial disease
Study dates	Not provided
Setting	1 centre in Canada
Number of participants	30 participants
Population	People with mitochondrial disease. Fifteen participants (9 female and 6 male) had MELAS, the remaining participants (11 female and 4 male) had other mitochondrial diseases. The mean age in the population with MELAS was 48 ±3 years and the mean age for the remaining participants was 56 ±3 years. Most participants had previously taken nutritional supplements including co-enzyme Q10 for several years. All supplements were stopped 6 weeks prior to starting the study. Participants were allowed to continue other medication
Inclusion criteria	Diagnosis of mitochondrial disease confirmed using a combination of clinical symptoms, fasting serum lactate concentration, muscle biopsy findings and mitochondrial DNA analysis
Exclusion criteria	No exclusion criteria provided
Intervention(s)	Co-enzyme Q10 at a dose of 600 mg twice daily^a
Comparator(s)	Placebo^a
Length of follow-up	60 days^b
Outcomes	Primary outcome not specified. The study assessed a variety of functional and biochemical measures including: Mitochondrial disease-specific activity of daily living and quality of life questionnaires ^c Forearm isometric fatigue test^d
Source of funding	Donation from an individual and family
Overall risk of bias/quality assessment (CASP RCT checklist)	Did the trial address a clearly focused issue?	No
	Was the assignment of participants to treatments randomised?	Yes
	Were participants, health workers and study personnel blinded?	Unclear^e
	Were the groups similar at the start of the trial?	Yes
	Aside from the experimental intervention, were the groups treated equally?	Yes
	Were all of the participants who entered the trial properly accounted for at its conclusion?	Yes
	How large was the treatment effect?	See table 9
	How precise was the estimate of the treatment effect?	See table 9
	Can the results be applied in your context? (or to the local population)	Unclear^f
	Were all clinically important outcomes considered?	Unclear^f
	Are the benefits worth the harms and costs?	See key points
Study limitations	Participants had previously received nutritional supplements including co-enzyme Q10 for several years Several outcomes were assessed and the primary endpoint was not defined No power calculation was presented in the paper The outcomes assessed may not be applicable to clinical practice Treatment and follow-up period of 60 days may be too short to fully assess effectiveness of co-enzyme Q10
Comments	^aParticipants took both co-enzyme Q10 and placebo for 60 days with a mean washout period of 67±8.3 days between each treatment. ^b Functional and biochemical measures were assessed after 60 days taking placebo and after 60 days taking co-enzyme Q10. Each testing day followed the same testing order. ^c Activities of daily living and quality of life questionnaires consisted of a series of questions that assessed capacity to perform tasks such as cooking and housework and perceived health and well-being measured on a visual-analogue scale from 0 to 100 mm. ^d Ninety second (9 second contraction and 1 second rest) isometric handgrip fatigue test. ^e The study was reported to be double-blind. Information is provided on how the co-enzyme Q10 capsules were blinded but insufficient information was provided in the paper to assess blinding of study personnel. ^f Insufficient information provided in paper to assess.
Abbreviations: HR, heart rate; MELAS, mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes; RCT, randomised controlled trial; RER; respiratory exchange rate; VE, minute ventilation; VO₂; oxygen uptake.